Hyperlipidemia constitutes a critical factor in the pathogenesis of vascular disease and gut microbiota dysbiosis.This study aims to investigate the role of sea buckthorn fruit oil(SBFO)in ameliorating hyperlipidemia,...Hyperlipidemia constitutes a critical factor in the pathogenesis of vascular disease and gut microbiota dysbiosis.This study aims to investigate the role of sea buckthorn fruit oil(SBFO)in ameliorating hyperlipidemia,modulating gut microbiota,and elucidating the underlying mechanisms of its lipid-lowering effects.SBFO intervention in hyperlipidemic mice significantly reduced body weight and visceral adiposity index while mitigating symptoms associated with hyperlipidemia,including dyslipidemia,infla mmation,liver damage,and endothelial dysfunction.Real-time quantitative PCR and Western blot analyses revealed that SBFO enhanced the response of free fatty acid oxidation and breakdown(adenosine 5'-monophosphateactivated protein kinaseα,carnitine palmitoyltransferase1a,peroxisome proliferator-activated receptorα,and peroxisome proliferator-activated receptorγ)while suppressing the synthesis of triglycerides and fatty acids(sterol-regulatory element binding protein 1,fatty acid synthase,and acetyl CoA carboxylase)at the gene and protein expression levels.Moreover,SBFO intervention enriched the gut microbiota of hyperlipidemic mice by increasing the relative abundances of Lactobacillus,Faecalibaculum,and Allobaculum,while decreasing the Firmicutes/Bacteroidetes ratio.These findings suggest that SBFO exhibits promising therapeutic potential in attenuating hyperlipidemia in mice through the regulation of lipid metabolism and modulation of gut microbiota.展开更多
Background:Sargentodoxae Caulis(SC)is the vine stem of Sargentodoxa Cuneata(Oliv.)Rehd.&E.H.Wilson in C.S.Sargent,and it in traditional Chinese medicine has been known for promoting blood circulation and removing ...Background:Sargentodoxae Caulis(SC)is the vine stem of Sargentodoxa Cuneata(Oliv.)Rehd.&E.H.Wilson in C.S.Sargent,and it in traditional Chinese medicine has been known for promoting blood circulation and removing blood stasis as recorded in the ancient book“Illustrated Classics of Materia Medica”.It has been used effectively to treat blood stasis too in modern clinical practice.However,the anti-hyperlipidemia effect of SC is not fully understood.This paper aims at exploring the use of SC stems to improve the balance of blood lipids in the body,and its new role in treating hyperlipidemia.Methods:The effects of SC extract on hyperlipidemia were explored by combining lipidomics and gut microbiota.Secondly,we explored the potential mechanism of SC in treating hyperlipidemia by pathway analysis.Results:The results showed that the stem extract of SC could restore the physiological and biochemical indices of hyperlipidemia in mice,as well as repair the morphological and structural damage to tissues.Compared to the Model group,the SC extract significantly reduced the liver index,epididymal fat index,and Lee’s index.It also significantly decreased serum levels of total cholesterol,triglycerides,low-density lipoprotein cholesterol,peroxisome proliferator-activated receptor gamma(PPAR-γ),D-lactate,and free fatty acids,while significantly increasing the relative content of peroxisome proliferator-activated receptor alpha(PPAR-α).These changes were statistically significant.Non-targeted lipidomics,based on LC-MS,were utilized to investigate the lipid metabolism characteristics in serum,liver,and epididymal fat of the subjects.It was observed that,compared to the blank group,the Model group exhibited significant changes primarily in glycerol lipids and glycerophospholipids.The treatment group also displayed alterations in these lipids.A total of 38,81,and 27 differential lipids were identified in serum,liver,and epididymal fat samples,respectively.Among these,14 common differential lipids were found in both serum and liver samples,and their KEGG enrichment pathways were largely consistent.Among them,the sphingolipid signaling pathway and the glycerophospholipid metabolic pathway were identified as key metabolic pathways that were regulated.Our gut microbiota analysis revealed that SC diminishes the abundance of Actinobacteria by altering the cecal flora in mice.Conclusion:This alteration leads to the downregulation of genes involved in triglyceride metabolism,which in turn changes lipid processing and reduces triglyceride levels.Consequently,SC effectively combats hyperlipidemia.Notably,SC impacts key metabolic pathways,including the sphingolipid signaling and glycerophospholipid metabolism.These findings underscore SC’s therapeutic potential,positioning it as a promising alternative for reducing the health risks associated with hyperlipidemia.展开更多
BACKGROUND The global incidence of hyperlipidemia has been increasing on an annual basis,concomitant with improvements in living standards and dietary changes.Hyperlipidemia is closely associated with the development ...BACKGROUND The global incidence of hyperlipidemia has been increasing on an annual basis,concomitant with improvements in living standards and dietary changes.Hyperlipidemia is closely associated with the development of numerous diseases,and in clinical cases,drug-induced cholestasis may lead to elevated serum cholesterol and triglyceride levels,a phenomenon known as secondary hyperlipidemia.Hyperlipidemia is recognized as a significant risk factor for the development of cardiovascular disease.Therefore,effective monitoring and control of lipid levels is crucial in the management of patients diagnosed with drug-induced cholestatic liver disease.CASE SUMMARY We present a special case of refractory hyperlipidemia associated with cholestatic liver disease in a 49-year-old woman.CONCLUSION In the treatment of clinical cases of drug-induced cholestatic liver disease and hyperlipidemia,it is essential for medical professionals to consider the patient’s overall condition,formulate an individualized treatment plan,and closely monitor the patient’s biochemical indices and clinical symptoms to ensure treatment efficacy and prognosis.展开更多
Fucoxanthin,a kind of exclusively algae-derived carotenoids,could reduce lipid content and regulate gut microbiota composition in obese mice,showing potential in preventing hyperlipidemia.This study aimed to illustrat...Fucoxanthin,a kind of exclusively algae-derived carotenoids,could reduce lipid content and regulate gut microbiota composition in obese mice,showing potential in preventing hyperlipidemia.This study aimed to illustrate fucoxanthin efficacy in modulating lipid metabolism in serum and liver of high-fat-induced hyperlipidemia mice,as well as investigate the underlying association with gut microbiota changes.Results showed that fucoxanthin significantly reduced body weight gain and body white fat of the mice.In the serum,total triglycerides(TG),total cholesterol(TC)contents were significantly decreased and high-densitylipoprotein cholesterol levels was significantly upregulated.Moreover,fucoxanthin remarkedly prevented lipid accumulation in the liver.Especially,metabolomics results showed that lipids and lipid-like molecules were significantly downregulated compared with the control,indicating the advance of hepatic lipid metabolism.Bile acids profile in the liver was also greatly changed by fucoxanthin.Meanwhile,fucoxanthin remodeled gut microbiota composition and promoted the relative abundance of Desulfovibrio,Blautia and Clostridia genera.Finally,correlation analysis revealed that these gut microbiota changes were closely related with hepatic metabolites/metabolism and serum lipids.Altogether,this study showed great potential of fucoxanthin in improving serum lipids profile,hepatic lipids and bile acids metabolism of hyperlipidemia mice,which was associated with gut microbiota alteration.展开更多
The aim of this study was to explore the mechanism of action of sea buckthorn polyphenols in the treatment of hyperlipidemia through network pharmacology and molecular docking.The TCMSP pharmacology database was used ...The aim of this study was to explore the mechanism of action of sea buckthorn polyphenols in the treatment of hyperlipidemia through network pharmacology and molecular docking.The TCMSP pharmacology database was used to screen the polyphenols present in sea buckthorn,and then the SwissTargetPrediction and Uniprot databases were used to obtain the potential targets of sea buckthorn polyphenols,which were supplemented by the literature.In total,7 polyphenols and 154 potential targets were obtained.Through GeneCards,OMIM database,1358 hyperlipidemia-related targets were collected.We found that there were 101 targets at the intersection of components and diseases.Through GO and KEGG enrichment analysis,27 core targets were obtained,which were AKT1,TNF,TP53,IL-6,etc.in order of degree value.174 pathways were obtained from KEGG enrichment analysis,including AGE-RAGE signaling pathway in diabetic complications,fl uid shear stress and atherosclerosis,lipid and atherosclerosis,etc.The molecular docking of the main components to the targets was performed using OpenBabelGUI,AutoDockTools-1.5.6 software.Finally,the results were visualized using Cytoscape 3.9.1 software.The molecular docking results showed that sea buckthorn polyphenols have good binding ability with the key targets.Among them,such as quercetin and kaempferol,have good binding ability with TNF,TP53 and IL-6.For example,TNF binds to quercetin with a binding energy of-5.34 kcal/mol and to kaempferol with a binding energy of-6.22 kcal/mol;TP53 binds to kaempferol with a binding energy of-5.32 kcal/mol;IL-6 binds to quercetin with a binding energy of-5.62 kcal/mol,etc.Therefore,the network pharmacology study showed that the treatment of hyperlipidemia by sea buckthorn polyphenols can be realized by multi-component-multi-target-multi-pathway together,which provides some reference for the later study of sea buckthorn polyphenols in the treatment of hyperlipidemia.展开更多
Objective:To explore the mechanism of action of Zangjiangzhi capsule(ZJZC)in treating hyperlipidemia(HLP).Methods:The components of ZJZC were analyzed and identified using ultra-high performance liquid chromatography ...Objective:To explore the mechanism of action of Zangjiangzhi capsule(ZJZC)in treating hyperlipidemia(HLP).Methods:The components of ZJZC were analyzed and identified using ultra-high performance liquid chromatography with Q-Exactive Orbitrap tandem mass spectrometry(UHPLC-Q-Exactive-Orbitrap-MS/MS).Network pharmacology analysis was used to explore the mechanism of action of ZJZC in HLP treatment.The SwissTargetPrediction database was used to predict compound targets,and GeneCards,DisGeNet,OMIM,and DRUGBANK databases were used to identify HLP-related targets.Proteineprotein interaction diagrams were constructed using the STRING database.The targets were subjected to gene ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.The“herbingredient-target”network was visualized using Cytoscape.Preliminary validation was performed using molecular docking and enzyme-linked immunosorbent assay.Results:Ninety compounds were identified in ZJZC,including 34 flavonoids,12 phenols,10 terpenoids,10 alkaloids,8 organic acids,8 anthraquinones,and 9 other compounds.In total,904 targets were identified for these compounds.Among them,158 targets intersected with the HLP target network.Network pharmacology analysis showed that MAPK1,PPAR-a,RXRA,HSP90AA1,PIK3R1,AKT1,PIK3CA,IL6,TNF,and ESR1 are the key targets of action.KEGG enrichment analysis identified 164 pathways.Among these,the AGE-RAGE signaling pathway in diabetic complications,lipid and atherosclerosis pathways,regulation of lipids in adipocytes,and insulin resistance are related to HLP.Molecular docking showed good affinity between the key targets and ingredients.Further,ZJZC treatment in mice resulted in lower expression of MAPK1 protein and increased expression of PPAR-a protein,which have been shown to be strongly associated with HLP.Conclusions:This study showed that ZJZC contains various active ingredients and can modulate multiple targets and pathways associated with HLP,providing evidence at the molecular level for its clinical application in the treatment of HLP.展开更多
Low-density lipoprotein cholesterol(LDL-C)is the most causal risk factor for atherosclerotic cardiovascular disease(ASCVD).Red yeast rice(RYR)is a nutraceutical widely used as a lipid-lowering dietary supplement.The m...Low-density lipoprotein cholesterol(LDL-C)is the most causal risk factor for atherosclerotic cardiovascular disease(ASCVD).Red yeast rice(RYR)is a nutraceutical widely used as a lipid-lowering dietary supplement.The main cholesterol-lower agents in RYR are monacolins,particularly monacolin K,a weak reversible inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase,whose daily consumption(up to 10 mg/day)reduces LDL-C plasma levels up to 34%within 6-8 weeks when compared to placebo.The reduction in LDL-C is often accompanied by lower levels of plasma apolipoprotein B,total cholesterol,matrix metalloproteinases 2 and 9,high-sensitivity C-reactive protein,non-high-density lipoprotein cholesterol,and blood pressure.RYR has also demonstrated favorable reductions of up to 45%compared to placebo in the risk of ASCVD events in secondary prevention studies.The mechanism of action is similar to statins.When consumed appropriately,RYR is associated with only minimal side effects.Mild myalgia may be seen in patients who cannot tolerate low-dose statins.In individuals with no additional ASCVD risk factors,RYR is a safe and effective supplement in treating mild to moderate hyperlipidemia.展开更多
Objective Recaticimab(SHR-1209)significantly reduces low-density lipoprotein cholesterol levels.However,its effect on glucose metabolism remains unclear.This study aimed to evaluate its effect on glycemic parameters i...Objective Recaticimab(SHR-1209)significantly reduces low-density lipoprotein cholesterol levels.However,its effect on glucose metabolism remains unclear.This study aimed to evaluate its effect on glycemic parameters in a Chinese population.Methods Recaticimab versus placebo was administered in a 5:1 ratio to 110 hyperlipidemia patients who were followed up for 24 weeks.Glycated hemoglobin(HbA1c)levels were measured at baseline every 12 weeks.Fasting plasma glucose(FPG)levels were measured at baseline at week 1,3,5,8,12,16,20,and 24.Repeated-measures mixed-effects models were used to determine the longitudinal association between reacticimab and FPG and HbA1c levels.Results Among the 81 participants with normal glucose metabolism,HbA1c levels significantly decreased(F=4.568,P=0.036).In the 29 participants with abnormal glucose metabolism,a significant time effect was observed for FPG levels(F=2.492,P=0.016).For participants with normal and abnormal glucose metabolism,no significant group×time interaction effects on FPG or HbA1c levels were identified.Conclusion Recaticimab showed no adverse glycemic effects in participants with normal or abnormal glucose metabolism,indicating its safety in patients with or without diabetes.展开更多
OBJECTIVE:To explore the clinical observation of white eye distribution characteristics of hyperlipidemic patients based on artificial intelligence digital eye diagnosis technology.METHODS:One hundred and fifty subjec...OBJECTIVE:To explore the clinical observation of white eye distribution characteristics of hyperlipidemic patients based on artificial intelligence digital eye diagnosis technology.METHODS:One hundred and fifty subjects were examined in the outpatient and inpatient departments of Guang'anmen Hospital of the China Academy of Traditional Chinese Medicine from 01 February 2022 to 01 February 2023,including 80 cases in the hyperlipidemic patient(HLP)group and 70 cases in the normal lipid level patient(NC)group.The two groups were collected and extracted by the artificial intelligence visual diagnostic instrument and analyzed by the MyEyeD-10 white eye shadowless imaging health intelligence analysis system.Finally,SPSS 26.0(Version X;IBM Corp.,Armonk,NY,USA)was used for statistical processing.RESULTS:Significant differences were noted in the scores of"spot"and"foggy"features between the two groups.Between groups,the"spot"feature score of the white eye morphology in the HLP group(11.07±3.22)was higher than that in the NC group(7.50±4.11)(P<0.01).Moreover,the"foggy"feature score of the eye morphology in the HLP group(8.37±2.25)was higher than that in the NC group(P<0.01),higher than that of the NC group(5.72±1.21)(P<0.05).There were significant differences in the"A"(stomach),"B","O"(spleen),and"M"(liver)eye-contact region scores between the two groups,and the"B","O"(spleen)and"M"(liver)eye-contact region scores were significantly different.The scores of the white eye channel region in the HLP group were significantly higher than those in the control group,with the"A","B",and"O"regions(P<0.01),"M"region(P<0.01),"A","B","O",and"M"region(P<0.01)."M"zone(P<0.05).The scores of"dull red"and"yellow"features were significantly different,and the scores of"dull red"and"yellow"colors of the white eye choroid in the HLP group were significantly higher than those in the HLP group.The scores of"dull red"and"yellow"were significantly higher in the HLP group than in the NC group(P<0.01).CONCLUSION:The morphological features of the white eye ocular image,the white eye chakra's color,and the bulbar conjunctiva's vascular zoning are closely related to hyperlipidemia.Importantly,these provide a reference for the objectivity and precision of the identification of Chinese medicine by looking at the eyes.展开更多
BACKGROUND Alagille syndrome is a rare autosomal dominant genetic disorder involving multiple organ systems.Its most common manifestations are chronic cholestasis caused by intrahepatic bile duct deficiency and severe...BACKGROUND Alagille syndrome is a rare autosomal dominant genetic disorder involving multiple organ systems.Its most common manifestations are chronic cholestasis caused by intrahepatic bile duct deficiency and severe hypercholesterolemia as a result of impaired cholesterol metabolism.This report describes a patient with Alagille syndrome in whom a JAG1 mutation was detected by whole-exome sequencing.CASE SUMMARY The patient presented with severe hypercholesterolemia,biliary and hepatic impairment,pruritus,and triangular facial features.Mutations in the JAG1 gene,which encodes the Notch signaling pathway,were detected by whole-exome sequencing,leading to a diagnosis of Alagille syndrome.The patient was treated using a combination of traditional Chinese and Western medicines.Her cholesterol levels,liver function,and pruritus subsequently improved.CONCLUSION The possibility of Alagille syndrome should be considered in children who present with abnormal liver function and severe hypercholesterolemia.Genetic testing is needed to screen for disease-causing mutations and the disease can be treated with Traditional Chinese medicine.展开更多
Background In recent years,the incidence of coronary heart disease(CHD)has continued to rise,and its comorbidity with hyperlipidemia significantly increases the mortality risk in patients.Statin monotherapy faces limi...Background In recent years,the incidence of coronary heart disease(CHD)has continued to rise,and its comorbidity with hyperlipidemia significantly increases the mortality risk in patients.Statin monotherapy faces limitations in efficacy for some patients and raises potential safety concerns.Ezetimibe,as a novel lipid-modulating agent,exhibits potential advantages in the treatment of hyperlipidemia.Based on this,the present study investigated the therapeutic efficacy of ezetimibe in CHD patients with hyperlipidemia,as well as its effects on lipid metabolism and the amelioration of atherosclerosis.Methods In this study,150 clinical cases with CHD and hyperlipidemia admitted in our hospital from July 2022 to July 2024 were collected for retrospective analysis.According to different treatment methods,they were randomly divided into the Atorvastatin group(control group,n=75)and the Atorvastatin+Ezetimibe group(experimental group,n=75).Control group received atorvastatin monotherapy,while experimental group were administered additional ezetimibe as an adjunct to the atorvastatin-based treatment regimen.The clinical efficacy of the two treatment groups was analyzed,including cardiac function-related parameters such as the cardiac index(CI),cardiac output(CO),left ventricular ejection fraction(LVEF)and left ventricular end-diastolic diameter(LVEDD)before and after treatment.The observed indicators encompassed coronary angiography findings,the Gensini score for assessing coronary stenosis severity,the inflammatory marker high-sensitivity C-reactive protein(hs-CRP),and lipid profile parameters including total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C).Additionally,the occurrence of adverse reactions during treatment was monitored.Results After treatment,the total effective rate in experimental group was significantly higher than that in control group,with a statistically significant difference(P<0.05).In the comparison of the baseline data,both groups showed marked improvements in CI,CO,LVEF,and HDL-C.However,at the same time points,the experimental group demonstrated significantly better results in these parameters than control group(P<0.05).Additionally,LVEDD,LDL-C,hs-CRP and Gensini scores were significantly reduced after treatment in both groups compared to pretreatment levels.Moreover,at identical time points,the aforementioned parameters in the experimental group demonstrated significantly greater reductions compared to control group(P<0.05).Regarding safety assessment,comparative analysis of adverse drug reaction(ADR)incidence rates between the two treatment groups revealed no statistically significant difference(P>0.05).Conclusions In patients with CHD complicated by hyperlipidemia,ezetimibe demonstrates significant therapeutic advantages.It effectively enhances treatment efficacy,regulates lipid profiles,improves cardiac function,and mitigates the progression of atherosclerosis.This regimen exhibits a favorable safety profile and holds substantial clinical value for both therapeutic processes and rehabilitation outcomes in this patient population.展开更多
The gut microbiota and it’s metabolism are vital targets of probiotics regulating high fat-diet(HFD)induced hyperlipidemia,which can relieve the pressure caused by the striking growth of sub-health people.Pediococcus...The gut microbiota and it’s metabolism are vital targets of probiotics regulating high fat-diet(HFD)induced hyperlipidemia,which can relieve the pressure caused by the striking growth of sub-health people.Pediococcus pentosaceus PP04(PP04)could colonize in intestine to regulate gut microbiota and it’s metabolites directly,the rebalanced intestinal flora mediated by PP04 could facilitate the secretion of short chain fatty acids to control body weight gain,PP04 intervention also changed bile acid(BA)profiles and enhanced the ileal concentrations of antagonists including tauro-α/β-muricholic acid sodium salt and ursodeoxycholic acid to inhibit intestinal farnesoid X receptor/fibroblast growth factor 15(FXR/FGF15)signaling coupled with the activation of hepatic FXR/small heterodimer partners signaling,which accelerated the hepatic BA de novo synthesis and excretion with feces to eliminate HFD caused hyperlipemia effectively.This study provided important evidence regarding PP04 as dietary supplement to relieve hyperlipidemia by influencing BA enterohepatic circulation.展开更多
Objective To observe the effect and explore the mechanism of acupuncture on hyperlipemia in mice. Methods One hundred and twenty male Kunming mice of clean grade were randomly divided into a normal group （40 mice）, ...Objective To observe the effect and explore the mechanism of acupuncture on hyperlipemia in mice. Methods One hundred and twenty male Kunming mice of clean grade were randomly divided into a normal group （40 mice）, a model group （40 mice）, an acupuncture group （20 mice）, and a drug group （20 mice）. The hyperlipidemia model was prepared in the latter 3 groups by feeding with high fat diet. After the successful modeling, bilateral ＂Fenglong＂ （丰隆 ST 40）, ＂Quchi＂ （曲池 LI 11）, and ＂Sanyinjiao＂ （三阴交 SP 6） were selected in the acupuncture group and Han＇s Acupuncture Stimulator was connected to intervent for 10 rain, once daily, for 10 successive days. Mice in the drug group were orally given Simvastatin, once daily, for 10 successive days. No intervention was given to the normal group and the model group. Serum contents of total cholesterol （TC）, triglyeeride （TG）, low-density lipoprotein cholesterol （LDL-C）, high-density lipoprotein cholesterol （HDL-C）, malondialdehyde （MDA）, nitric oxide （NO）, endothelin （ET）, and the activity of superoxide dismutase （SOD） were detected. Results The serum contents of TG, TC and LDL-C in the model group detected on the 15th day were all higher than those of the normal group [（1.31±0.32） mmol/L vs （0.70±0.21） retool/L, （5.72±0.85） mmol/L vs （3.08±0.74） retool/L, （2.68±0.55） mmol/L vs （1.83±0.36） retool/L, respectively]. The serum content of HDL-C in the model group was lower than that in the normal group [（0.60±0.26） mmol/L vs （0.94±0.30） mmol/L], showing successful modeling. On the lOth day of successful modeling, the serum contents of MDA and ET in the acupuncture group were lower than those in the model group [（21.58±3.54） p, mol/mL vs （29.94±2.79） p, mol/mL, （44.51±5.23） pg/mL vs （67.07±11.98） pg/mL]. The serum SOD activities and NO content in the acupuncture group were higher than those in the model gropu [（264.57±14.46） U/mL vs （222.66±25.48） U/mL, （85.02±10.06） μmol/L vs （63.83±9.19） μmol/L]. Conclusion Acupuncture could lower serum contents of MDA and ET, improve SOD activities and NO content, showing acupuncture could fight against lipid peroxidation, clear free radicals, regulate as well as ameliorate the metabolic balance of free radicals, and protect the vascular endothelium in hyperlipidemia mice.展开更多
Objective To examine the relationship between occurrence of hyperlipidemia, plasma homocysteine and polymorphisms of methylenetetra hydrofolate reductase （MTHFR） gene and methionine synthase （MS） gene. Methods A t...Objective To examine the relationship between occurrence of hyperlipidemia, plasma homocysteine and polymorphisms of methylenetetra hydrofolate reductase （MTHFR） gene and methionine synthase （MS） gene. Methods A total of 192 hyperlipidemia patients were selected and divided into hypercholesterolemia group, hypertriglyceridemia group, and combined hyperlipidemia group. Another 208 normal individuals were selected as control. Total plasma homocysteine （tHcy） concentration was measured by high-performance liquid chromatography （HPLC）. Lipid profiles were measured for all subjects The polymorphisms of MTHFR gene C677T and MS gene A2756G were analyzed by PCR-RFLP. Results The tHcy concentration in the combined hyperlipidemia patients was significantly higher than that in the control （15.95μmol/L vs 13.43 μmol/L, P〈0.05）. The prevalence of hyperhomocysteinemia （HHcy） in the combined hyperlipidemia group was significantly higher than that in the control （42.2% vs 23.0%, P=0.015）, with the odds ratio （OR） of 3.339 （95%CI： 1.260-8.849）. The hyperlipidemia patients with HHcy had a higher concentration of total cholesterol （TC） than that in the normal tHcy patients （5.67±0.95 mmol/L vs 5.47±0.92 retool/L, P=0.034）. There was no significant difference in genotype or allele frequencies of MTHFR C677T between the hyperlipidemic and control groups. The hyperlipidemia patients with MTHFR CT/TT genotype had a higher concentration of triglyceride （TG） than those with CC genotype （2.24±1.75 mmol/L vs 1.87±0.95 mmol/L, P〈0.05）. Individuals with CT/TT genotype had a higher concentration of tHcy than those with 677CC genotype both in the hyperlipidemia group （12.61±1.24μmol/L vs 11.20±1.37 μmol/L, P〈0.05） and in the control group （14.04±1.48 μmol/L vs 12.61±1.24 μmol/L, P〈0.05）. The percentage of MS 2756 GG/AG genotype in the combined hyperlipidemia group was significantly higher than that in the control （26.7% vs 13.0%, P=0.012）, with the OR of 3.121 （95%C1： 1.288-7.65/）. The hyperlipidemia patients with MS 2756AG/GG genotype had a higher concentration of TC （5.87±0.89 mmol/L vs 5.46±0.93 retool/L, P〈0.05） and LDL-C （3.29±0.81 mmol/L vs 2.94±0.85 retool/L, P〈0.05） than those with AA genotype. However, individuals with 2756AG/GG genotype showed no significant difference in tHcy among those with AA genotype. Conclusion HHcy and MS A2756G mutation may be the risk factors for combined hyperlipidemia. Further study is needed to confirm the role of HHcy and MS A2756G mutation in the development of hyperlipidemia.展开更多
AIM: To investigate the efficacy and safety of n-3 polyunsaturated fatty acids (PUFA) from seal oils for patients with nonalcoholic fatty liver disease (NAFLD) associated with hyperlipidemia. METHODS: One hundred and ...AIM: To investigate the efficacy and safety of n-3 polyunsaturated fatty acids (PUFA) from seal oils for patients with nonalcoholic fatty liver disease (NAFLD) associated with hyperlipidemia. METHODS: One hundred and forty-four patients with NAFLD associated with hyperlipidemia were included in the 24-wk, randomized, controlled trial. The patients were randomized into two groups. Group A (n = 72) received recommended diet and 2 g n-3 PUFA from seal oils, three times a day. Group B (n = 72) received recommended diet and 2 g placebo, three times a day. Primary endpoints were fatty liver assessed by symptom scores, liver alanine aminotransferase (ALT) and serum lipid levels after 8, 12, 16, and 24 wk. Hepatic fat inf iltration was detected by ultrasonography at weeks 12 and 24 after treatment. RESULTS: A total of 134 patients (66 in group A, 68 in group B) were included in the study except for 10 patients who were excluded from the study. After 24 wk of treatment, no change was observed in body weight, fasting blood glucose (FBG), renal function and blood cells of these patients. Total symptom scores, ALT and triglyceride (TG) levels decreased more significantly in group A than in group B (P < 0.05). As expected, there was a tendency toward improvement in aspartate aminotransferase (AST), γ-glutamyltranspeptidase (GGT), and total cholesterol (TCHO) and high- density lipoprotein (HDL) cholesterol levels (P < 0.05) after administration in the two groups. However, no significant differences were found between the two groups. The values of low-density lipoprotein (LDL) were significantly improved in group A (P < 0.05), but no significant change was found in group B at different time points and after a 24-wk treatment. After treatment, complete fatty liver regression was observed in 19.70% (13/66) of the patients, and an overall reduction was found in 53.03% (35/66) of the patients in group A. In contrast, in group B, only f ive patients (7.35%, 5/68) achieved complete fatty liver regression (P = 0.04), whereas 24 patients (35.29%, 24/68) had a certain improvement in fatty liver (P = 0.04). No serious adverse events occurred in all the patients who completed the treatment. CONCLUSION: Our results indicate that n-3 PUFA from seal oils is safe and effi cacious for patients with NAFLD associated with hyperlipidemia and can improve their total symptom scores, ALT, serum lipid levels and normalization of ultrasonographic evidence. Further study is needed to confi rm these results.展开更多
OBJECTIVE:To assess the clinical effectiveness and adverse effects of Yinchenwuling powder(YCWLP)in the treatment of hyperlipidemia using Meta-analysis.METHODS:Seven electronic databases were searched for randomized c...OBJECTIVE:To assess the clinical effectiveness and adverse effects of Yinchenwuling powder(YCWLP)in the treatment of hyperlipidemia using Meta-analysis.METHODS:Seven electronic databases were searched for randomized controlled trials designed to evaluate the clinical effectiveness of YCWLP for hyperlipidemia published in any language prior to February 2015.Two reviewers independently identified articles,extracted data,assessed quality,and cross-checked the results.Revman 5.3 was used to analyze the data.RESULTS:Only five randomized controlled trials with poor methodology were included in the analy-sis.The five trials compared YCWLP with conventional lipid-lowering drugs.Meta-analysis indicated that YCWLP was more effective at the levels of total cholesterol and triglycerides,while increasing the level of high-density lipoprotein cholesterol without serious adverse effects.However,it was not more effective than lipid-lowering drugs in reducing low-density lipoprotein cholesterol and improving hemorheology.CONCLUSION:YCWLP appeared to improve lipid levels.However,given the high risk of bias among the trials,we could not conclude that YCWLP was beneficial to patients with hyperlipidemia.More rigorous trials are required to provide stronger evidence for the conclusion.展开更多
AIM:To investigate the correlation of hyperlipemia(HL) and acute cerebral ischemia/reperfusion(I/R) injury on liver damage and its mechanism.METHODS:Rats were divided into 4 groups:control,HL,I/R and HL+I/R.After the ...AIM:To investigate the correlation of hyperlipemia(HL) and acute cerebral ischemia/reperfusion(I/R) injury on liver damage and its mechanism.METHODS:Rats were divided into 4 groups:control,HL,I/R and HL+I/R.After the induction of HL via a high-fat diet for 18 wk,middle cerebral artery occlusion was followed by 24 h of reperfusion to capture I/R.Serum alanine transaminase(ALT) and aspartate aminotransferase(AST) were analyzed as part of liver function tests and liver damage was further assessed by histological examination.Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling(TUNEL) assay.The expression of genes related to apoptosis(caspase-3,bcl-2) was assayed by immunohistochemistry and Western blotting.Serum tumor necrosis factor-(TNF-),interleukin-1(IL-1) and liver mitochondrial superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA) and Ca 2+ levels were measured to determine inflammatory and oxidative/antioxidative status respectively.Microsomal hydroxylase activity of the cytochrome P450 2E1(CYP2E1)-containing enzyme was measured with aniline as the substrate,and CYP2E1 expression in the liver tissue and microsome was determined by immunohistochemistry and Western blotting respectively.RESULTS:HL alone induced by high-fat diet for 18 wk resulted in liver damage,indicated by histopathological analysis,and a considerable increase in serum ALT(25.13 ± 16.90 vs 9.56 ± 1.99,P < 0.01) and AST levels(18.01 ± 10.00 vs 11.33 ± 4.17,P < 0.05) compared with control.Moreover,HL alone induced hepatocyte apoptosis,which was determined by increased TUNEL-positive cells(4.47 ± 0.45 vs 1.5 ± 0.22,P < 0.01),higher caspase-3 and lower bcl-2 expression.Interestingly,compared with those in control,HL or I/R groups,massive increases of serum ALT(93.62 ± 24.00 vs 9.56 ± 1.99,25.13 ± 16.90 or 12.93 ± 6.14,P < 0.01) and AST(82.32 ± 26.92 vs 11.33 ± 4.17,18.01 ± 10.00 or 14.00 ± 6.19,P < 0.01) levels in HL+I/R group were observed suggesting severe liver damage,which was confirmed by liver histology.In addition,HL combined with I/R also caused significantly increased hepatocyte apoptosis,as evidenced by increased TUNEL-positive cells(6.20 ± 0.29 vs 1.5 ± 0.22,4.47 ± 0.45 or 1.97 ± 0.47,P < 0.01),elevated expression of caspase-3 and lower expression of bcl-2.Furthermore,when compared to HL or I/R alone,HL plus I/R enhanced serum TNF-,IL-1,liver mitochondrial MDA and Ca 2+ levels,suppressed SOD and GSH-Px in liver mitochondria,and markedly up-regulated the activity(11.76 ± 2.36 vs 4.77 ± 2.31 or 3.11 ± 1.35,P < 0.01) and expression(3.24 ± 0.38 vs 1.98 ± 0.88 or 1.72 ± 0.58,P < 0.01) of CYP2E1 in liver.CONCLUSION:The coexistence of HL and acute cerebral I/R induces severe liver damage,suggesting that cerebral ischemic stroke would exaggerate the damage of liver caused by HL.This effect is possibly due to en-hanced CYP2E1 induction which further promotes oxidative damage,inflammation and hepatocyte apoptosis.展开更多
AIM： To investigate the effects of hyperlipidemia on acute pancreatitis （AP） and the possible mechanisms. METHODS： Rat models of hyperlipidemia and AP were established by Triton WR1339 and cerulein respectively. H...AIM： To investigate the effects of hyperlipidemia on acute pancreatitis （AP） and the possible mechanisms. METHODS： Rat models of hyperlipidemia and AP were established by Triton WR1339 and cerulein respectively. Human albumin was used to treat AP complicated by hyperlipidemia. In each group, we compared the histological score, volume of ascites, ratio of pancreatic wet/dry weight, serum amylase （AMY） and pancreatic acinar cell apoptosis. The level of protein kinase C （PKC） membrane translocation in pancreatic tissue was detected by Western blot.RESULTS： In the hyperlipidemia model established by Triton WR1339, triglyceride （TG） increased remarkably and reached its peak 6 h after injection, and most rats developed mild acute pancreatitis. Histological score, volume of ascites, ratio of wet/dry weight and serum AMY in AP animals with hyperlipidemia were obviously higher than those in AP animals （P 〈 0.05） and decreased after albumin therapy but not significantly （P 〉 0.05）. Apoptotic cells detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling （TUNEL） increased in AP animals with hyperlipidemia and did not change distinctly after albumin therapy. PKC membrane translocation level increased in AP animals with hyperlipidemia and decreased remarkably after albumin therapy （P 〈 0.05）.CONCLUSION： Hyperlipidemia may induce AP or intensify pancreatic injury. Albumin therapy can not alleviate pancreatic lesion effectively. PKC activation may be one mechanism by which AP is intensified by hyperlipidemia.展开更多
Electroacupuncture(EA)has been shown to reduce blood lipid level and improve cerebral ischemia in rats with hyperlipemia complicated by cerebral ischemia.However,there are few studies on the results and mechanism of t...Electroacupuncture(EA)has been shown to reduce blood lipid level and improve cerebral ischemia in rats with hyperlipemia complicated by cerebral ischemia.However,there are few studies on the results and mechanism of the effect of EA in reducing blood lipid level or promoting neural repair after stroke in hyperlipidemic subjects.In this study,EA was applied to a rat model of hyperlipidemia and middle cerebral artery thrombosis and the condition of neurons and astrocytes after hippocampal injury was assessed.Except for the normal group,rats in other groups were fed a high-fat diet throughout the whole experiment.Hyperlipidemia models were established in rats fed a high-fat diet for 6 weeks.Middle cerebral artery thrombus models were induced by pasting 50%FeCl3 filter paper on the left middle cerebral artery for 20 minutes on day 50 as the model group.EA1 group rats received EA at bilateral ST40(Fenglong)for 7 days before the thrombosis.Rats in the EA1 and EA2 groups received EA at GV20(Baihui)and bilateral ST40 for 14 days after model establishment.Neuronal health was assessed by hematoxylin-eosin staining in the brain.Hyperlipidemia was assessed by biochemical methods that measured total cholesterol,triglyceride,low-density lipoprotein and high-density lipoprotein in blood sera.Behavioral analysis was used to confirm the establishment of the model.Immunohistochemical methods were used to detect the expression of glial fibrillary acidic protein and nerve growth factor in the hippocampal CA1 region.The results demonstrated that,compared with the model group,blood lipid levels significantly decreased,glial fibrillary acidic protein immunoreactivity was significantly weakened and nerve growth factor immunoreactivity was significantly enhanced in the EA1 and EA2 groups.The repair effect was superior in the EA1 group than in the EA2 group.These findings confirm that EA can reduce blood lipid,inhibit glial fibrillary acidic protein expression and promote nerve growth factor expression in the hippocampal CA1 region after hyperlipidemia and middle cerebral artery thrombosis.All experimental procedures and protocols were approved by the Animal Use and Management Committee of Beijing University of Chinese Medicine,China(approval No.BUCM-3-2018022802-1002)on April 12,2018.展开更多
OBJECTIVE： To explore the plasma metabolite pro- files in patients with the syndrome of phlegm and blood stasis in hyperlipidemia and atherosclerosis （As）, and to search for the metabolic biomarkers of the syndrome...OBJECTIVE： To explore the plasma metabolite pro- files in patients with the syndrome of phlegm and blood stasis in hyperlipidemia and atherosclerosis （As）, and to search for the metabolic biomarkers of the syndrome. METHODS： The plasma metabolite profiles of 31 patients with the syndrome of phlegm and blood stasis in hyperlipidemia and As, 6 patients with syn- dromes without phlegm and blood stasis, and 10 healthy subjects were analyzed by gas chromatog- raphy-mass spectrometry （GC-MS）. Partial least squares-discriminant analyses （PLS-DA） were used to carry out the pattern-recognition analyses of the data. The plasma metabolic biomarkers of patients were obtained by variable importance plot value （VlP value） and Student＇s t-test. The structures ofbiomarkers were defined by the National Institute of Standards and Technology （NIST） database. RESULTS： PLS-DA score plots of plasma metabo- Iomes did not show overlap between the phlegm-blood stasis syndrome group and syn- dromes without phlegm and blood stasis group, whereas significant differences in the concentra- tions in the plasma of 5 metabolites were found （P〈 0.05）. They were identified as urine, isoleucine, gluc- uronic acid, palmitic acid and glycerol by searching in NIST database. The concentrations of four metab- olites in the plasma of patients with syndrome of phlegm and blood stasis were higher than those with syndromes without phlegm and blood stasis, whereas the glycerol concentration was lower. CONCLUSION： Compared with patients with syn- dromes without phlegm and blood stasis, five me- tabolites showed abnormal levels in patients with the syndrome of phlegm and blood stasis. These metabolites could be diagnostic and prognostic biomarkers.展开更多
基金supported by the National Natural Science Foundation of China(31201416)Programme of Introducing Talents of Discipline to Universities(B17018)。
文摘Hyperlipidemia constitutes a critical factor in the pathogenesis of vascular disease and gut microbiota dysbiosis.This study aims to investigate the role of sea buckthorn fruit oil(SBFO)in ameliorating hyperlipidemia,modulating gut microbiota,and elucidating the underlying mechanisms of its lipid-lowering effects.SBFO intervention in hyperlipidemic mice significantly reduced body weight and visceral adiposity index while mitigating symptoms associated with hyperlipidemia,including dyslipidemia,infla mmation,liver damage,and endothelial dysfunction.Real-time quantitative PCR and Western blot analyses revealed that SBFO enhanced the response of free fatty acid oxidation and breakdown(adenosine 5'-monophosphateactivated protein kinaseα,carnitine palmitoyltransferase1a,peroxisome proliferator-activated receptorα,and peroxisome proliferator-activated receptorγ)while suppressing the synthesis of triglycerides and fatty acids(sterol-regulatory element binding protein 1,fatty acid synthase,and acetyl CoA carboxylase)at the gene and protein expression levels.Moreover,SBFO intervention enriched the gut microbiota of hyperlipidemic mice by increasing the relative abundances of Lactobacillus,Faecalibaculum,and Allobaculum,while decreasing the Firmicutes/Bacteroidetes ratio.These findings suggest that SBFO exhibits promising therapeutic potential in attenuating hyperlipidemia in mice through the regulation of lipid metabolism and modulation of gut microbiota.
基金supported by the Science and Technology Program of Tianjin in China(No.23ZYJDSS00030)the Public Applied Technology Research Project of Zhejiang Province(No.LGD22H090010)。
文摘Background:Sargentodoxae Caulis(SC)is the vine stem of Sargentodoxa Cuneata(Oliv.)Rehd.&E.H.Wilson in C.S.Sargent,and it in traditional Chinese medicine has been known for promoting blood circulation and removing blood stasis as recorded in the ancient book“Illustrated Classics of Materia Medica”.It has been used effectively to treat blood stasis too in modern clinical practice.However,the anti-hyperlipidemia effect of SC is not fully understood.This paper aims at exploring the use of SC stems to improve the balance of blood lipids in the body,and its new role in treating hyperlipidemia.Methods:The effects of SC extract on hyperlipidemia were explored by combining lipidomics and gut microbiota.Secondly,we explored the potential mechanism of SC in treating hyperlipidemia by pathway analysis.Results:The results showed that the stem extract of SC could restore the physiological and biochemical indices of hyperlipidemia in mice,as well as repair the morphological and structural damage to tissues.Compared to the Model group,the SC extract significantly reduced the liver index,epididymal fat index,and Lee’s index.It also significantly decreased serum levels of total cholesterol,triglycerides,low-density lipoprotein cholesterol,peroxisome proliferator-activated receptor gamma(PPAR-γ),D-lactate,and free fatty acids,while significantly increasing the relative content of peroxisome proliferator-activated receptor alpha(PPAR-α).These changes were statistically significant.Non-targeted lipidomics,based on LC-MS,were utilized to investigate the lipid metabolism characteristics in serum,liver,and epididymal fat of the subjects.It was observed that,compared to the blank group,the Model group exhibited significant changes primarily in glycerol lipids and glycerophospholipids.The treatment group also displayed alterations in these lipids.A total of 38,81,and 27 differential lipids were identified in serum,liver,and epididymal fat samples,respectively.Among these,14 common differential lipids were found in both serum and liver samples,and their KEGG enrichment pathways were largely consistent.Among them,the sphingolipid signaling pathway and the glycerophospholipid metabolic pathway were identified as key metabolic pathways that were regulated.Our gut microbiota analysis revealed that SC diminishes the abundance of Actinobacteria by altering the cecal flora in mice.Conclusion:This alteration leads to the downregulation of genes involved in triglyceride metabolism,which in turn changes lipid processing and reduces triglyceride levels.Consequently,SC effectively combats hyperlipidemia.Notably,SC impacts key metabolic pathways,including the sphingolipid signaling and glycerophospholipid metabolism.These findings underscore SC’s therapeutic potential,positioning it as a promising alternative for reducing the health risks associated with hyperlipidemia.
基金Supported by Beijing Municipal Health Commission High-Level Public Health Technical Personnel Construction Project,No.discipline leader-03-26Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support,No.ZLRK202301+1 种基金Beijing Hospitals Authority“Peak”Talent Training Program,No.DFL20241803The National Key Research and Development Program,No.2023YFC2306901 and No.2023YFC2308105.
文摘BACKGROUND The global incidence of hyperlipidemia has been increasing on an annual basis,concomitant with improvements in living standards and dietary changes.Hyperlipidemia is closely associated with the development of numerous diseases,and in clinical cases,drug-induced cholestasis may lead to elevated serum cholesterol and triglyceride levels,a phenomenon known as secondary hyperlipidemia.Hyperlipidemia is recognized as a significant risk factor for the development of cardiovascular disease.Therefore,effective monitoring and control of lipid levels is crucial in the management of patients diagnosed with drug-induced cholestatic liver disease.CASE SUMMARY We present a special case of refractory hyperlipidemia associated with cholestatic liver disease in a 49-year-old woman.CONCLUSION In the treatment of clinical cases of drug-induced cholestatic liver disease and hyperlipidemia,it is essential for medical professionals to consider the patient’s overall condition,formulate an individualized treatment plan,and closely monitor the patient’s biochemical indices and clinical symptoms to ensure treatment efficacy and prognosis.
基金funded by the National Natural Science Foundation of China(31901624)the Key-Area Research and Development Program of Guangdong Province(2018B020206001)+2 种基金Guangdong Province Zhujiang Talent Program(2019ZT08H476)Shenzhen Science and Technology Program(KQTD20180412181334790)the Innovation Team Project of Universities in Guangdong Province(2020KCXTD023)。
文摘Fucoxanthin,a kind of exclusively algae-derived carotenoids,could reduce lipid content and regulate gut microbiota composition in obese mice,showing potential in preventing hyperlipidemia.This study aimed to illustrate fucoxanthin efficacy in modulating lipid metabolism in serum and liver of high-fat-induced hyperlipidemia mice,as well as investigate the underlying association with gut microbiota changes.Results showed that fucoxanthin significantly reduced body weight gain and body white fat of the mice.In the serum,total triglycerides(TG),total cholesterol(TC)contents were significantly decreased and high-densitylipoprotein cholesterol levels was significantly upregulated.Moreover,fucoxanthin remarkedly prevented lipid accumulation in the liver.Especially,metabolomics results showed that lipids and lipid-like molecules were significantly downregulated compared with the control,indicating the advance of hepatic lipid metabolism.Bile acids profile in the liver was also greatly changed by fucoxanthin.Meanwhile,fucoxanthin remodeled gut microbiota composition and promoted the relative abundance of Desulfovibrio,Blautia and Clostridia genera.Finally,correlation analysis revealed that these gut microbiota changes were closely related with hepatic metabolites/metabolism and serum lipids.Altogether,this study showed great potential of fucoxanthin in improving serum lipids profile,hepatic lipids and bile acids metabolism of hyperlipidemia mice,which was associated with gut microbiota alteration.
基金supported by 2024 Liaoning Province Graduate Education Teaching Reform Research Project(LNYJG2024251).
文摘The aim of this study was to explore the mechanism of action of sea buckthorn polyphenols in the treatment of hyperlipidemia through network pharmacology and molecular docking.The TCMSP pharmacology database was used to screen the polyphenols present in sea buckthorn,and then the SwissTargetPrediction and Uniprot databases were used to obtain the potential targets of sea buckthorn polyphenols,which were supplemented by the literature.In total,7 polyphenols and 154 potential targets were obtained.Through GeneCards,OMIM database,1358 hyperlipidemia-related targets were collected.We found that there were 101 targets at the intersection of components and diseases.Through GO and KEGG enrichment analysis,27 core targets were obtained,which were AKT1,TNF,TP53,IL-6,etc.in order of degree value.174 pathways were obtained from KEGG enrichment analysis,including AGE-RAGE signaling pathway in diabetic complications,fl uid shear stress and atherosclerosis,lipid and atherosclerosis,etc.The molecular docking of the main components to the targets was performed using OpenBabelGUI,AutoDockTools-1.5.6 software.Finally,the results were visualized using Cytoscape 3.9.1 software.The molecular docking results showed that sea buckthorn polyphenols have good binding ability with the key targets.Among them,such as quercetin and kaempferol,have good binding ability with TNF,TP53 and IL-6.For example,TNF binds to quercetin with a binding energy of-5.34 kcal/mol and to kaempferol with a binding energy of-6.22 kcal/mol;TP53 binds to kaempferol with a binding energy of-5.32 kcal/mol;IL-6 binds to quercetin with a binding energy of-5.62 kcal/mol,etc.Therefore,the network pharmacology study showed that the treatment of hyperlipidemia by sea buckthorn polyphenols can be realized by multi-component-multi-target-multi-pathway together,which provides some reference for the later study of sea buckthorn polyphenols in the treatment of hyperlipidemia.
基金supported by the National Natural Science Foundation of China(22067016)the Project of Qinghai Outstanding Youth Fund Project(2023-ZJ-964J).
文摘Objective:To explore the mechanism of action of Zangjiangzhi capsule(ZJZC)in treating hyperlipidemia(HLP).Methods:The components of ZJZC were analyzed and identified using ultra-high performance liquid chromatography with Q-Exactive Orbitrap tandem mass spectrometry(UHPLC-Q-Exactive-Orbitrap-MS/MS).Network pharmacology analysis was used to explore the mechanism of action of ZJZC in HLP treatment.The SwissTargetPrediction database was used to predict compound targets,and GeneCards,DisGeNet,OMIM,and DRUGBANK databases were used to identify HLP-related targets.Proteineprotein interaction diagrams were constructed using the STRING database.The targets were subjected to gene ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.The“herbingredient-target”network was visualized using Cytoscape.Preliminary validation was performed using molecular docking and enzyme-linked immunosorbent assay.Results:Ninety compounds were identified in ZJZC,including 34 flavonoids,12 phenols,10 terpenoids,10 alkaloids,8 organic acids,8 anthraquinones,and 9 other compounds.In total,904 targets were identified for these compounds.Among them,158 targets intersected with the HLP target network.Network pharmacology analysis showed that MAPK1,PPAR-a,RXRA,HSP90AA1,PIK3R1,AKT1,PIK3CA,IL6,TNF,and ESR1 are the key targets of action.KEGG enrichment analysis identified 164 pathways.Among these,the AGE-RAGE signaling pathway in diabetic complications,lipid and atherosclerosis pathways,regulation of lipids in adipocytes,and insulin resistance are related to HLP.Molecular docking showed good affinity between the key targets and ingredients.Further,ZJZC treatment in mice resulted in lower expression of MAPK1 protein and increased expression of PPAR-a protein,which have been shown to be strongly associated with HLP.Conclusions:This study showed that ZJZC contains various active ingredients and can modulate multiple targets and pathways associated with HLP,providing evidence at the molecular level for its clinical application in the treatment of HLP.
文摘Low-density lipoprotein cholesterol(LDL-C)is the most causal risk factor for atherosclerotic cardiovascular disease(ASCVD).Red yeast rice(RYR)is a nutraceutical widely used as a lipid-lowering dietary supplement.The main cholesterol-lower agents in RYR are monacolins,particularly monacolin K,a weak reversible inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase,whose daily consumption(up to 10 mg/day)reduces LDL-C plasma levels up to 34%within 6-8 weeks when compared to placebo.The reduction in LDL-C is often accompanied by lower levels of plasma apolipoprotein B,total cholesterol,matrix metalloproteinases 2 and 9,high-sensitivity C-reactive protein,non-high-density lipoprotein cholesterol,and blood pressure.RYR has also demonstrated favorable reductions of up to 45%compared to placebo in the risk of ASCVD events in secondary prevention studies.The mechanism of action is similar to statins.When consumed appropriately,RYR is associated with only minimal side effects.Mild myalgia may be seen in patients who cannot tolerate low-dose statins.In individuals with no additional ASCVD risk factors,RYR is a safe and effective supplement in treating mild to moderate hyperlipidemia.
基金funded by Jiangsu Hengrui Pharmaceutical Co.,Ltd.(formerly,Jiangsu Hengrui Medicine Co.,Ltd.).
文摘Objective Recaticimab(SHR-1209)significantly reduces low-density lipoprotein cholesterol levels.However,its effect on glucose metabolism remains unclear.This study aimed to evaluate its effect on glycemic parameters in a Chinese population.Methods Recaticimab versus placebo was administered in a 5:1 ratio to 110 hyperlipidemia patients who were followed up for 24 weeks.Glycated hemoglobin(HbA1c)levels were measured at baseline every 12 weeks.Fasting plasma glucose(FPG)levels were measured at baseline at week 1,3,5,8,12,16,20,and 24.Repeated-measures mixed-effects models were used to determine the longitudinal association between reacticimab and FPG and HbA1c levels.Results Among the 81 participants with normal glucose metabolism,HbA1c levels significantly decreased(F=4.568,P=0.036).In the 29 participants with abnormal glucose metabolism,a significant time effect was observed for FPG levels(F=2.492,P=0.016).For participants with normal and abnormal glucose metabolism,no significant group×time interaction effects on FPG or HbA1c levels were identified.Conclusion Recaticimab showed no adverse glycemic effects in participants with normal or abnormal glucose metabolism,indicating its safety in patients with or without diabetes.
基金Supported by National Natural Science Foundation of China:Study on the Mechanism of Improving Cardiac Remodelling in Post-infarction Ischaemic Cardiomyopathy through lncRNA-Maternally Expressed Gene3/miR-223/Stromal Interaction Molecule 1 Calcium Signalling Axis by Activate Blood and Reassure Formula (No. 81973682)National Social Science Fund:Study on the Verification and Construction of the Theory System of Sanjiao Phase Fire and Yang Support Under the View of Civilisation Traceability (No. 21VJXG037)+1 种基金First Published:a Randomised Controlled Study of Fuyang Qiangxin Tang in the Treatment of Moderate to Severe Heart Failure (2024-1-4151)Project for Enhancing Clinical Research and Achievement Transformation Capabilities of High-Level Traditional Chinese Medicine Hospitals:Evaluation of the Efficacy and Preclinical Study of Fuyang Qiangxin Granules, a Traditional Chinese Medicine for Heart Failure (HLCMHPP2023045)
文摘OBJECTIVE:To explore the clinical observation of white eye distribution characteristics of hyperlipidemic patients based on artificial intelligence digital eye diagnosis technology.METHODS:One hundred and fifty subjects were examined in the outpatient and inpatient departments of Guang'anmen Hospital of the China Academy of Traditional Chinese Medicine from 01 February 2022 to 01 February 2023,including 80 cases in the hyperlipidemic patient(HLP)group and 70 cases in the normal lipid level patient(NC)group.The two groups were collected and extracted by the artificial intelligence visual diagnostic instrument and analyzed by the MyEyeD-10 white eye shadowless imaging health intelligence analysis system.Finally,SPSS 26.0(Version X;IBM Corp.,Armonk,NY,USA)was used for statistical processing.RESULTS:Significant differences were noted in the scores of"spot"and"foggy"features between the two groups.Between groups,the"spot"feature score of the white eye morphology in the HLP group(11.07±3.22)was higher than that in the NC group(7.50±4.11)(P<0.01).Moreover,the"foggy"feature score of the eye morphology in the HLP group(8.37±2.25)was higher than that in the NC group(P<0.01),higher than that of the NC group(5.72±1.21)(P<0.05).There were significant differences in the"A"(stomach),"B","O"(spleen),and"M"(liver)eye-contact region scores between the two groups,and the"B","O"(spleen)and"M"(liver)eye-contact region scores were significantly different.The scores of the white eye channel region in the HLP group were significantly higher than those in the control group,with the"A","B",and"O"regions(P<0.01),"M"region(P<0.01),"A","B","O",and"M"region(P<0.01)."M"zone(P<0.05).The scores of"dull red"and"yellow"features were significantly different,and the scores of"dull red"and"yellow"colors of the white eye choroid in the HLP group were significantly higher than those in the HLP group.The scores of"dull red"and"yellow"were significantly higher in the HLP group than in the NC group(P<0.01).CONCLUSION:The morphological features of the white eye ocular image,the white eye chakra's color,and the bulbar conjunctiva's vascular zoning are closely related to hyperlipidemia.Importantly,these provide a reference for the objectivity and precision of the identification of Chinese medicine by looking at the eyes.
基金Natural Science Foundation of Hebei Province,China,No.H2020209160Scientific Research Projects in Chinese Medicine of Hebei Province,China,No.2019168.
文摘BACKGROUND Alagille syndrome is a rare autosomal dominant genetic disorder involving multiple organ systems.Its most common manifestations are chronic cholestasis caused by intrahepatic bile duct deficiency and severe hypercholesterolemia as a result of impaired cholesterol metabolism.This report describes a patient with Alagille syndrome in whom a JAG1 mutation was detected by whole-exome sequencing.CASE SUMMARY The patient presented with severe hypercholesterolemia,biliary and hepatic impairment,pruritus,and triangular facial features.Mutations in the JAG1 gene,which encodes the Notch signaling pathway,were detected by whole-exome sequencing,leading to a diagnosis of Alagille syndrome.The patient was treated using a combination of traditional Chinese and Western medicines.Her cholesterol levels,liver function,and pruritus subsequently improved.CONCLUSION The possibility of Alagille syndrome should be considered in children who present with abnormal liver function and severe hypercholesterolemia.Genetic testing is needed to screen for disease-causing mutations and the disease can be treated with Traditional Chinese medicine.
文摘Background In recent years,the incidence of coronary heart disease(CHD)has continued to rise,and its comorbidity with hyperlipidemia significantly increases the mortality risk in patients.Statin monotherapy faces limitations in efficacy for some patients and raises potential safety concerns.Ezetimibe,as a novel lipid-modulating agent,exhibits potential advantages in the treatment of hyperlipidemia.Based on this,the present study investigated the therapeutic efficacy of ezetimibe in CHD patients with hyperlipidemia,as well as its effects on lipid metabolism and the amelioration of atherosclerosis.Methods In this study,150 clinical cases with CHD and hyperlipidemia admitted in our hospital from July 2022 to July 2024 were collected for retrospective analysis.According to different treatment methods,they were randomly divided into the Atorvastatin group(control group,n=75)and the Atorvastatin+Ezetimibe group(experimental group,n=75).Control group received atorvastatin monotherapy,while experimental group were administered additional ezetimibe as an adjunct to the atorvastatin-based treatment regimen.The clinical efficacy of the two treatment groups was analyzed,including cardiac function-related parameters such as the cardiac index(CI),cardiac output(CO),left ventricular ejection fraction(LVEF)and left ventricular end-diastolic diameter(LVEDD)before and after treatment.The observed indicators encompassed coronary angiography findings,the Gensini score for assessing coronary stenosis severity,the inflammatory marker high-sensitivity C-reactive protein(hs-CRP),and lipid profile parameters including total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C).Additionally,the occurrence of adverse reactions during treatment was monitored.Results After treatment,the total effective rate in experimental group was significantly higher than that in control group,with a statistically significant difference(P<0.05).In the comparison of the baseline data,both groups showed marked improvements in CI,CO,LVEF,and HDL-C.However,at the same time points,the experimental group demonstrated significantly better results in these parameters than control group(P<0.05).Additionally,LVEDD,LDL-C,hs-CRP and Gensini scores were significantly reduced after treatment in both groups compared to pretreatment levels.Moreover,at identical time points,the aforementioned parameters in the experimental group demonstrated significantly greater reductions compared to control group(P<0.05).Regarding safety assessment,comparative analysis of adverse drug reaction(ADR)incidence rates between the two treatment groups revealed no statistically significant difference(P>0.05).Conclusions In patients with CHD complicated by hyperlipidemia,ezetimibe demonstrates significant therapeutic advantages.It effectively enhances treatment efficacy,regulates lipid profiles,improves cardiac function,and mitigates the progression of atherosclerosis.This regimen exhibits a favorable safety profile and holds substantial clinical value for both therapeutic processes and rehabilitation outcomes in this patient population.
基金supported by the Jilin Province Science and Technology Plan Project(20230402032GH)the Jilin Province Science and Technology Development Project(20220508115RC).
文摘The gut microbiota and it’s metabolism are vital targets of probiotics regulating high fat-diet(HFD)induced hyperlipidemia,which can relieve the pressure caused by the striking growth of sub-health people.Pediococcus pentosaceus PP04(PP04)could colonize in intestine to regulate gut microbiota and it’s metabolites directly,the rebalanced intestinal flora mediated by PP04 could facilitate the secretion of short chain fatty acids to control body weight gain,PP04 intervention also changed bile acid(BA)profiles and enhanced the ileal concentrations of antagonists including tauro-α/β-muricholic acid sodium salt and ursodeoxycholic acid to inhibit intestinal farnesoid X receptor/fibroblast growth factor 15(FXR/FGF15)signaling coupled with the activation of hepatic FXR/small heterodimer partners signaling,which accelerated the hepatic BA de novo synthesis and excretion with feces to eliminate HFD caused hyperlipemia effectively.This study provided important evidence regarding PP04 as dietary supplement to relieve hyperlipidemia by influencing BA enterohepatic circulation.
基金Supported by Key Project Foundation of Hebei Administration of TCM:2009058
文摘Objective To observe the effect and explore the mechanism of acupuncture on hyperlipemia in mice. Methods One hundred and twenty male Kunming mice of clean grade were randomly divided into a normal group （40 mice）, a model group （40 mice）, an acupuncture group （20 mice）, and a drug group （20 mice）. The hyperlipidemia model was prepared in the latter 3 groups by feeding with high fat diet. After the successful modeling, bilateral ＂Fenglong＂ （丰隆 ST 40）, ＂Quchi＂ （曲池 LI 11）, and ＂Sanyinjiao＂ （三阴交 SP 6） were selected in the acupuncture group and Han＇s Acupuncture Stimulator was connected to intervent for 10 rain, once daily, for 10 successive days. Mice in the drug group were orally given Simvastatin, once daily, for 10 successive days. No intervention was given to the normal group and the model group. Serum contents of total cholesterol （TC）, triglyeeride （TG）, low-density lipoprotein cholesterol （LDL-C）, high-density lipoprotein cholesterol （HDL-C）, malondialdehyde （MDA）, nitric oxide （NO）, endothelin （ET）, and the activity of superoxide dismutase （SOD） were detected. Results The serum contents of TG, TC and LDL-C in the model group detected on the 15th day were all higher than those of the normal group [（1.31±0.32） mmol/L vs （0.70±0.21） retool/L, （5.72±0.85） mmol/L vs （3.08±0.74） retool/L, （2.68±0.55） mmol/L vs （1.83±0.36） retool/L, respectively]. The serum content of HDL-C in the model group was lower than that in the normal group [（0.60±0.26） mmol/L vs （0.94±0.30） mmol/L], showing successful modeling. On the lOth day of successful modeling, the serum contents of MDA and ET in the acupuncture group were lower than those in the model group [（21.58±3.54） p, mol/mL vs （29.94±2.79） p, mol/mL, （44.51±5.23） pg/mL vs （67.07±11.98） pg/mL]. The serum SOD activities and NO content in the acupuncture group were higher than those in the model gropu [（264.57±14.46） U/mL vs （222.66±25.48） U/mL, （85.02±10.06） μmol/L vs （63.83±9.19） μmol/L]. Conclusion Acupuncture could lower serum contents of MDA and ET, improve SOD activities and NO content, showing acupuncture could fight against lipid peroxidation, clear free radicals, regulate as well as ameliorate the metabolic balance of free radicals, and protect the vascular endothelium in hyperlipidemia mice.
基金supported by Beijing Natural Science Foundation, China (No. 7072044).
文摘Objective To examine the relationship between occurrence of hyperlipidemia, plasma homocysteine and polymorphisms of methylenetetra hydrofolate reductase （MTHFR） gene and methionine synthase （MS） gene. Methods A total of 192 hyperlipidemia patients were selected and divided into hypercholesterolemia group, hypertriglyceridemia group, and combined hyperlipidemia group. Another 208 normal individuals were selected as control. Total plasma homocysteine （tHcy） concentration was measured by high-performance liquid chromatography （HPLC）. Lipid profiles were measured for all subjects The polymorphisms of MTHFR gene C677T and MS gene A2756G were analyzed by PCR-RFLP. Results The tHcy concentration in the combined hyperlipidemia patients was significantly higher than that in the control （15.95μmol/L vs 13.43 μmol/L, P〈0.05）. The prevalence of hyperhomocysteinemia （HHcy） in the combined hyperlipidemia group was significantly higher than that in the control （42.2% vs 23.0%, P=0.015）, with the odds ratio （OR） of 3.339 （95%CI： 1.260-8.849）. The hyperlipidemia patients with HHcy had a higher concentration of total cholesterol （TC） than that in the normal tHcy patients （5.67±0.95 mmol/L vs 5.47±0.92 retool/L, P=0.034）. There was no significant difference in genotype or allele frequencies of MTHFR C677T between the hyperlipidemic and control groups. The hyperlipidemia patients with MTHFR CT/TT genotype had a higher concentration of triglyceride （TG） than those with CC genotype （2.24±1.75 mmol/L vs 1.87±0.95 mmol/L, P〈0.05）. Individuals with CT/TT genotype had a higher concentration of tHcy than those with 677CC genotype both in the hyperlipidemia group （12.61±1.24μmol/L vs 11.20±1.37 μmol/L, P〈0.05） and in the control group （14.04±1.48 μmol/L vs 12.61±1.24 μmol/L, P〈0.05）. The percentage of MS 2756 GG/AG genotype in the combined hyperlipidemia group was significantly higher than that in the control （26.7% vs 13.0%, P=0.012）, with the OR of 3.121 （95%C1： 1.288-7.65/）. The hyperlipidemia patients with MS 2756AG/GG genotype had a higher concentration of TC （5.87±0.89 mmol/L vs 5.46±0.93 retool/L, P〈0.05） and LDL-C （3.29±0.81 mmol/L vs 2.94±0.85 retool/L, P〈0.05） than those with AA genotype. However, individuals with 2756AG/GG genotype showed no significant difference in tHcy among those with AA genotype. Conclusion HHcy and MS A2756G mutation may be the risk factors for combined hyperlipidemia. Further study is needed to confirm the role of HHcy and MS A2756G mutation in the development of hyperlipidemia.
基金Supported by Shanghai Natural Science Fund of China, 05ZR14156
文摘AIM: To investigate the efficacy and safety of n-3 polyunsaturated fatty acids (PUFA) from seal oils for patients with nonalcoholic fatty liver disease (NAFLD) associated with hyperlipidemia. METHODS: One hundred and forty-four patients with NAFLD associated with hyperlipidemia were included in the 24-wk, randomized, controlled trial. The patients were randomized into two groups. Group A (n = 72) received recommended diet and 2 g n-3 PUFA from seal oils, three times a day. Group B (n = 72) received recommended diet and 2 g placebo, three times a day. Primary endpoints were fatty liver assessed by symptom scores, liver alanine aminotransferase (ALT) and serum lipid levels after 8, 12, 16, and 24 wk. Hepatic fat inf iltration was detected by ultrasonography at weeks 12 and 24 after treatment. RESULTS: A total of 134 patients (66 in group A, 68 in group B) were included in the study except for 10 patients who were excluded from the study. After 24 wk of treatment, no change was observed in body weight, fasting blood glucose (FBG), renal function and blood cells of these patients. Total symptom scores, ALT and triglyceride (TG) levels decreased more significantly in group A than in group B (P < 0.05). As expected, there was a tendency toward improvement in aspartate aminotransferase (AST), γ-glutamyltranspeptidase (GGT), and total cholesterol (TCHO) and high- density lipoprotein (HDL) cholesterol levels (P < 0.05) after administration in the two groups. However, no significant differences were found between the two groups. The values of low-density lipoprotein (LDL) were significantly improved in group A (P < 0.05), but no significant change was found in group B at different time points and after a 24-wk treatment. After treatment, complete fatty liver regression was observed in 19.70% (13/66) of the patients, and an overall reduction was found in 53.03% (35/66) of the patients in group A. In contrast, in group B, only f ive patients (7.35%, 5/68) achieved complete fatty liver regression (P = 0.04), whereas 24 patients (35.29%, 24/68) had a certain improvement in fatty liver (P = 0.04). No serious adverse events occurred in all the patients who completed the treatment. CONCLUSION: Our results indicate that n-3 PUFA from seal oils is safe and effi cacious for patients with NAFLD associated with hyperlipidemia and can improve their total symptom scores, ALT, serum lipid levels and normalization of ultrasonographic evidence. Further study is needed to confi rm these results.
基金Supported by the Chinese National Natural Science Foundation Key Project(Identification of the Molecular Signature Contributing to the Susceptibility of Phlegmatic Hygrosis Constitution to Metabolic Syndrome,No.81030064)
文摘OBJECTIVE:To assess the clinical effectiveness and adverse effects of Yinchenwuling powder(YCWLP)in the treatment of hyperlipidemia using Meta-analysis.METHODS:Seven electronic databases were searched for randomized controlled trials designed to evaluate the clinical effectiveness of YCWLP for hyperlipidemia published in any language prior to February 2015.Two reviewers independently identified articles,extracted data,assessed quality,and cross-checked the results.Revman 5.3 was used to analyze the data.RESULTS:Only five randomized controlled trials with poor methodology were included in the analy-sis.The five trials compared YCWLP with conventional lipid-lowering drugs.Meta-analysis indicated that YCWLP was more effective at the levels of total cholesterol and triglycerides,while increasing the level of high-density lipoprotein cholesterol without serious adverse effects.However,it was not more effective than lipid-lowering drugs in reducing low-density lipoprotein cholesterol and improving hemorheology.CONCLUSION:YCWLP appeared to improve lipid levels.However,given the high risk of bias among the trials,we could not conclude that YCWLP was beneficial to patients with hyperlipidemia.More rigorous trials are required to provide stronger evidence for the conclusion.
文摘AIM:To investigate the correlation of hyperlipemia(HL) and acute cerebral ischemia/reperfusion(I/R) injury on liver damage and its mechanism.METHODS:Rats were divided into 4 groups:control,HL,I/R and HL+I/R.After the induction of HL via a high-fat diet for 18 wk,middle cerebral artery occlusion was followed by 24 h of reperfusion to capture I/R.Serum alanine transaminase(ALT) and aspartate aminotransferase(AST) were analyzed as part of liver function tests and liver damage was further assessed by histological examination.Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling(TUNEL) assay.The expression of genes related to apoptosis(caspase-3,bcl-2) was assayed by immunohistochemistry and Western blotting.Serum tumor necrosis factor-(TNF-),interleukin-1(IL-1) and liver mitochondrial superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA) and Ca 2+ levels were measured to determine inflammatory and oxidative/antioxidative status respectively.Microsomal hydroxylase activity of the cytochrome P450 2E1(CYP2E1)-containing enzyme was measured with aniline as the substrate,and CYP2E1 expression in the liver tissue and microsome was determined by immunohistochemistry and Western blotting respectively.RESULTS:HL alone induced by high-fat diet for 18 wk resulted in liver damage,indicated by histopathological analysis,and a considerable increase in serum ALT(25.13 ± 16.90 vs 9.56 ± 1.99,P < 0.01) and AST levels(18.01 ± 10.00 vs 11.33 ± 4.17,P < 0.05) compared with control.Moreover,HL alone induced hepatocyte apoptosis,which was determined by increased TUNEL-positive cells(4.47 ± 0.45 vs 1.5 ± 0.22,P < 0.01),higher caspase-3 and lower bcl-2 expression.Interestingly,compared with those in control,HL or I/R groups,massive increases of serum ALT(93.62 ± 24.00 vs 9.56 ± 1.99,25.13 ± 16.90 or 12.93 ± 6.14,P < 0.01) and AST(82.32 ± 26.92 vs 11.33 ± 4.17,18.01 ± 10.00 or 14.00 ± 6.19,P < 0.01) levels in HL+I/R group were observed suggesting severe liver damage,which was confirmed by liver histology.In addition,HL combined with I/R also caused significantly increased hepatocyte apoptosis,as evidenced by increased TUNEL-positive cells(6.20 ± 0.29 vs 1.5 ± 0.22,4.47 ± 0.45 or 1.97 ± 0.47,P < 0.01),elevated expression of caspase-3 and lower expression of bcl-2.Furthermore,when compared to HL or I/R alone,HL plus I/R enhanced serum TNF-,IL-1,liver mitochondrial MDA and Ca 2+ levels,suppressed SOD and GSH-Px in liver mitochondria,and markedly up-regulated the activity(11.76 ± 2.36 vs 4.77 ± 2.31 or 3.11 ± 1.35,P < 0.01) and expression(3.24 ± 0.38 vs 1.98 ± 0.88 or 1.72 ± 0.58,P < 0.01) of CYP2E1 in liver.CONCLUSION:The coexistence of HL and acute cerebral I/R induces severe liver damage,suggesting that cerebral ischemic stroke would exaggerate the damage of liver caused by HL.This effect is possibly due to en-hanced CYP2E1 induction which further promotes oxidative damage,inflammation and hepatocyte apoptosis.
基金Supported by the Key Program of Beijing Academy of Health, No. 1998-11-2001-09
文摘AIM： To investigate the effects of hyperlipidemia on acute pancreatitis （AP） and the possible mechanisms. METHODS： Rat models of hyperlipidemia and AP were established by Triton WR1339 and cerulein respectively. Human albumin was used to treat AP complicated by hyperlipidemia. In each group, we compared the histological score, volume of ascites, ratio of pancreatic wet/dry weight, serum amylase （AMY） and pancreatic acinar cell apoptosis. The level of protein kinase C （PKC） membrane translocation in pancreatic tissue was detected by Western blot.RESULTS： In the hyperlipidemia model established by Triton WR1339, triglyceride （TG） increased remarkably and reached its peak 6 h after injection, and most rats developed mild acute pancreatitis. Histological score, volume of ascites, ratio of wet/dry weight and serum AMY in AP animals with hyperlipidemia were obviously higher than those in AP animals （P 〈 0.05） and decreased after albumin therapy but not significantly （P 〉 0.05）. Apoptotic cells detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling （TUNEL） increased in AP animals with hyperlipidemia and did not change distinctly after albumin therapy. PKC membrane translocation level increased in AP animals with hyperlipidemia and decreased remarkably after albumin therapy （P 〈 0.05）.CONCLUSION： Hyperlipidemia may induce AP or intensify pancreatic injury. Albumin therapy can not alleviate pancreatic lesion effectively. PKC activation may be one mechanism by which AP is intensified by hyperlipidemia.
基金This study was funded by the National Natural Science Foundation of China,No.81470200(to XJR).
文摘Electroacupuncture(EA)has been shown to reduce blood lipid level and improve cerebral ischemia in rats with hyperlipemia complicated by cerebral ischemia.However,there are few studies on the results and mechanism of the effect of EA in reducing blood lipid level or promoting neural repair after stroke in hyperlipidemic subjects.In this study,EA was applied to a rat model of hyperlipidemia and middle cerebral artery thrombosis and the condition of neurons and astrocytes after hippocampal injury was assessed.Except for the normal group,rats in other groups were fed a high-fat diet throughout the whole experiment.Hyperlipidemia models were established in rats fed a high-fat diet for 6 weeks.Middle cerebral artery thrombus models were induced by pasting 50%FeCl3 filter paper on the left middle cerebral artery for 20 minutes on day 50 as the model group.EA1 group rats received EA at bilateral ST40(Fenglong)for 7 days before the thrombosis.Rats in the EA1 and EA2 groups received EA at GV20(Baihui)and bilateral ST40 for 14 days after model establishment.Neuronal health was assessed by hematoxylin-eosin staining in the brain.Hyperlipidemia was assessed by biochemical methods that measured total cholesterol,triglyceride,low-density lipoprotein and high-density lipoprotein in blood sera.Behavioral analysis was used to confirm the establishment of the model.Immunohistochemical methods were used to detect the expression of glial fibrillary acidic protein and nerve growth factor in the hippocampal CA1 region.The results demonstrated that,compared with the model group,blood lipid levels significantly decreased,glial fibrillary acidic protein immunoreactivity was significantly weakened and nerve growth factor immunoreactivity was significantly enhanced in the EA1 and EA2 groups.The repair effect was superior in the EA1 group than in the EA2 group.These findings confirm that EA can reduce blood lipid,inhibit glial fibrillary acidic protein expression and promote nerve growth factor expression in the hippocampal CA1 region after hyperlipidemia and middle cerebral artery thrombosis.All experimental procedures and protocols were approved by the Animal Use and Management Committee of Beijing University of Chinese Medicine,China(approval No.BUCM-3-2018022802-1002)on April 12,2018.
基金Supported by the National Natural Science Foundation of China for "Combining proteomics and metabolomics to research biological markers group of hyperlipoidemia and arteriosclerosis with the syndrome of phlegm-blood stasis" (No.90709008)National Science and Technology Major Projects for "Major New Drugs Innovation and Development"(2009ZX09502-018)
文摘OBJECTIVE： To explore the plasma metabolite pro- files in patients with the syndrome of phlegm and blood stasis in hyperlipidemia and atherosclerosis （As）, and to search for the metabolic biomarkers of the syndrome. METHODS： The plasma metabolite profiles of 31 patients with the syndrome of phlegm and blood stasis in hyperlipidemia and As, 6 patients with syn- dromes without phlegm and blood stasis, and 10 healthy subjects were analyzed by gas chromatog- raphy-mass spectrometry （GC-MS）. Partial least squares-discriminant analyses （PLS-DA） were used to carry out the pattern-recognition analyses of the data. The plasma metabolic biomarkers of patients were obtained by variable importance plot value （VlP value） and Student＇s t-test. The structures ofbiomarkers were defined by the National Institute of Standards and Technology （NIST） database. RESULTS： PLS-DA score plots of plasma metabo- Iomes did not show overlap between the phlegm-blood stasis syndrome group and syn- dromes without phlegm and blood stasis group, whereas significant differences in the concentra- tions in the plasma of 5 metabolites were found （P〈 0.05）. They were identified as urine, isoleucine, gluc- uronic acid, palmitic acid and glycerol by searching in NIST database. The concentrations of four metab- olites in the plasma of patients with syndrome of phlegm and blood stasis were higher than those with syndromes without phlegm and blood stasis, whereas the glycerol concentration was lower. CONCLUSION： Compared with patients with syn- dromes without phlegm and blood stasis, five me- tabolites showed abnormal levels in patients with the syndrome of phlegm and blood stasis. These metabolites could be diagnostic and prognostic biomarkers.
