BACKGROUND Colorectal cancer(CRC)is a major cause of cancer-related mortality,with limited therapeutic options for advanced stages.Simvastatin,primarily used to lower cholesterol,has shown potential as an anticancer a...BACKGROUND Colorectal cancer(CRC)is a major cause of cancer-related mortality,with limited therapeutic options for advanced stages.Simvastatin,primarily used to lower cholesterol,has shown potential as an anticancer agent.It may exert its effects by inhibiting SERPINE1,a protein implicated in CRC progression,and activating the cyclic guanosine monophosphate-protein kinase G(cGMP/PKG)signaling pathway.Given these findings,this study hypothesizes that simvastatin inhibits CRC cell proliferation and migration by downregulating SERPINE1 and activating the cGMP/PKG pathway,offering a novel therapeutic strategy for CRC management.AIM To study the effects of simvastatin on the function of colon cancer cells and to uncover the underlying mechanisms.METHODS NCM460,HCT-116,and SW620 cell lines were used for in vitro experiments with simvastatin at doses of 20μM,40μM,and 80μM.The Stitch database was used to analyze the target genes of simvastatin,whereas STRING was used to investigate SERPINE1 and its related pathways.HCT-116 and SW620 cells were transfected with single-cell RNA sequencing reveals SERPINE1 with or without Rp-8-Br-cGMP(a PKG inhibitor).Cell toxicity,proliferation,and migration were evaluated using the cell counting kit-8,colony formation,and Transwell assays,respectively.Apoptosis was analyzed via flow cytometry,and levels of reactive oxygen species(ROS),malondialdehyde(MDA),glutathione(GSH),and ferrous ion(Fe^(2+))were detected using commercial kits.Real-time polymerase chain reaction and western blotting were used to analyze gene expression.RESULTS Simvastatin dose-dependently inhibited the proliferation and migration of HCT-116 and SW620 cells while promoting apoptosis.It downregulated Ki-67,proliferating cell nuclear antigen,MMP2,and MMP9,and upregulated Bax,particularly at higher doses.Simvastatin increased the ROS,MDA,and Fe^(2+)levels while decreasing the GSH levels.It downregulated SLC7A11 and ferroportin and upregulated TRF1.SERPINE1 was identified as a core target,with related genes enriched in the cGMP/PKG pathway.SERPINE1 knockdown increased GUCY1B1 and PRKG1 levels,decreased cell viability,and altered oxidative stress markers,with the effects being reversed by Rp-8-Br-cGMP.CONCLUSION Simvastatin effectively inhibited the proliferation and migration of colon cancer cells and promoted apoptosis through the modulation of key targets,such as SERPINE1 and the cGMP/PKG signaling pathway.展开更多
Background:Both simvastatin and metformin have demonstrated potential efficacy in osteoporosis(OP)treatment.However,there is a lack of systematic studies comparing their anti-osteoporotic effects.This study aims to co...Background:Both simvastatin and metformin have demonstrated potential efficacy in osteoporosis(OP)treatment.However,there is a lack of systematic studies comparing their anti-osteoporotic effects.This study aims to compare the effects of simvastatin and metformin on OP through Mendelian randomization(MR)studies and animal experiments.Methods:Initially,we will analyze the causal impact of simvastatin or metformin treatment on OP prevalence and three common clinical OP diagnostic markers(bone mineral density(BMD),serum osteocalcin(OCN),and tartrate-resistant acid phosphatase(TRAP)levels)using genome-wide association study(GWAS)summary statistics.Additionally,we established animal models to further analyze and compare the anti-osteoporosis effects of simvastatin and metformin.8 male C57BL/6J mice(3-month-old)and 24 male C57BL/6J mice(18-month-old)were treated with simvastatin or metformin for 12 weeks.OP pathology was assessed using histology,immunohistochemistry,biomechanical tests,micro-computed tomography,and osteogenic differentiation assays.Results:In the MR analysis,metformin treatment was significantly associated with lower OP prevalence(OR(95%CI)=0.933(0.902–0.965),β=-0.0694,P<0.001)and higher BMD(OR(95%CI)=3.719(1.750–7.908),β=1.3136,P<0.001).In the animal experiment,both drugs increased bone mass,improved bone microstructure,and promoted osteoblast differentiation.However,metformin appeared more effective in several aspects.It significantly inhibited bone marrow adipocyte and osteoclast differentiation in aged mice compared to simvastatin.Additionally,metformin better promoted the expression of osteoprotegerin(OPG)and collagen type I(Col-I)in bone tissue and maintained the structure and biomechanical properties of cancellous bone.Conclusion:Both drugs significantly preserved bone homeostasis.Particularly,compared with simvastatin,metformin exhibited superior effects in inhibiting adipogenesis,enhancing the OPG/RANKL pathway,and promoting cancellous bone reconstruction.Metformin may serve as a valuable adjunct in preventing and treating OP in the elderly.展开更多
The total ginsenosides of ginseng fruit are the main constituents of Zhenyuan capsule,which is mainly used for the treatment of cardiovascular diseases.It has been reported that ginsenoside can affect the activity of ...The total ginsenosides of ginseng fruit are the main constituents of Zhenyuan capsule,which is mainly used for the treatment of cardiovascular diseases.It has been reported that ginsenoside can affect the activity of CYP450 enzymes.Zhenyuan capsule and simvastatin may interact with each other through CYP3 A4 mediation,then affect the efficacy and even produce adverse reactions.However,no studies have investigated the effects of Zhenyuan capsule on the pharmacokinetics of simvastatin and its active metabolites.In this study,liquid chromatography–electrospray ionization–mass spectrometry(LC-MS/MS)was used to detect the pharmacokinetics of simvastatin and its active metabolites-simvastatin acid with or without Zhenyuan capsule in rats.Compared with the simvastatin alone,the pharmacokinetic parameters of simvastatin and simvastatin acid were significantly different in AUC0–24 and AUC0–∞,and they were decreased in varying degrees(P<0.05).It appeared that the Zhenyuan capsule might increase the activity of CYP3 A4 to some extent.展开更多
Objective:To investigate the preventive and therapeutic effect and mechanism of simvastatin on secondary inflammatory damage of rats with cerebral hemorrhage.Methods:Sixty SD rat aged 9-12 weeks were chosen and divide...Objective:To investigate the preventive and therapeutic effect and mechanism of simvastatin on secondary inflammatory damage of rats with cerebral hemorrhage.Methods:Sixty SD rat aged 9-12 weeks were chosen and divided into the control group,model group and simvastatintreated group randomly with 20 rats in each group.Rats in the model group and simvastatintreated group were infused with autologous fresh uncoagulated blood to the right brain tissue of the basal ganglia to build the cerebral hemorrhage model,while rats in the control group were treated with the same amount of normal saline.Then,rats in the simvastatin-treated group were given a gavage of 3 mg/kg of simvastatin once a day after modeling.Rats in the three groups were given nerve dysfunction score(NDS) and wet-dry weighting method was used to detect the brain water content(BWC) of brain tissues around the lesion of the rats.Then Nissl staining was conducted and the undamaged neurons were counted.Immunohistochemical SP method was applied to count the number of NF-d the immuno fluorκB,TLR4 and IL-1escence method wasβ positive cells in brain tissues around the lesions,an employed to determine the expression levels of NF-κB,TLR4 and IL-1me points were aβ proteins.Results:The NDS results of the simvastatin-treated group at all till significantly higher than those of the model group(P < 0.05);the BWC values of the simvastatin-treated group at all time points were all significantly lower than those of the model group at the same periods(P < 0.05);the number of the undamaged neurons around the lesions of the simvastatin-treated group at all time points were all significantly higher than those of the model group(P < 0.05);seven days after treatment,the number of the NF-κB,TLR4 and IL-1β positive cells in brain tissues around the lesions of the simvastatin-treated group were all significantly lower than those of the model group(P < 0.05),and its expression levels of NF-ower than those of the model group(κB,TLR4 and IL-1P < 0.05).Conclusioβ protein were also significantly lns:Simvastatin can inhibit the expressions of NF-κB,TLR4 and IL-1β proteins in rats with cerebral hemorrhage,and protect neurons and reduce secondary inflammatory damages by down-regulating the above protein-mediated inflammatory responses.展开更多
Aim To determine the effect of local simvastatin application on the mRNA expression level of transforming growth factor-β1 （TGF-β1）, bone morphogenetic protein-2 （BMP-2） and vascular endothelial growth factor （...Aim To determine the effect of local simvastatin application on the mRNA expression level of transforming growth factor-β1 （TGF-β1）, bone morphogenetic protein-2 （BMP-2） and vascular endothelial growth factor （VEGF） in the tooth sockets of rat. Methodology Forty-eight male Wistar rats were randomly divided into experimental and control groups （n=24）. Polylactic acid/polyglycolic acid copolymer carriers, with or without simvastatin, were implanted into extraction sockets of right mandibular incisors. The expression of TGF-β1, BMP-2 and VEGF mRNA was determined by in situ hybridization in the tooth extraction socket at five days, one week, two weeks and four weeks after implantation. Results The fusiform stroma cells in the tooth extraction socket began to express TGF-β1, BMP-2 and VEGF mRNA in both experimental and control groups from one week after tooth extraction until the end of experiment. The expression of TGF-131 and BMP-2 mRNA in the experimental group was significantly up-regulated after one, two and four weeks, and expression of VEGF mRNA was significantly increased after one and two weeks compared with that in the control group. Conclusion The findings indicate that local administration of simvastatin can influence alveolar bone remodeling by regulating the expression of a school of growth factors which are crucial to osteogenesis in the tooth extraction socket.展开更多
Cardiovascular disease(CVD) is the most common cause of death in patients with non-alcoholic fatty liver disease(NAFLD). New therapeutic strategies which have the potential for slowing down the evolution of NAFLD and ...Cardiovascular disease(CVD) is the most common cause of death in patients with non-alcoholic fatty liver disease(NAFLD). New therapeutic strategies which have the potential for slowing down the evolution of NAFLD and reducing CVD-related mortality are urgently needed. Statins are well recognized in the treatment of dyslipidemia, but their use in the treatment of NAFLD is limited due to the safety concerns. Ilexgenin A(IA) is one of the main bioactive compounds in ‘Shan-lv-cha', an herbal tea commonly used in China. In the present study, we investigated the possible synergistic therapeutic effects of IA and simvastatin(SV) on NAFLD. IA or SV showed beneficial effects on the rats with NAFLD by lowering the liver weight, liver index and plasma levels of alanine aminotransferase and aspartate aminotransferase, regulating abnormal metabolism of lipids and ameliorating steatosis in liver. IA significantly enhanced the hypolipidemic and anti-inflammation effects of SV. Furthermore, a sensitive, accurate, convenient and reproducible LC-MS method was developed to investigate the effects of IA on the pharmacokinetics of SV. No significant changes were observed in pharmacokinetic parameters of SV and simvastatin hydroxy acid in the IA plus SV co-treated group in comparison with those in the group treated with SV alone. The m RNA levels and activity of CYP3 A1 were not altered by IA. In conclusion, the results obtained from the present study should be helpful for further clinical application of SV and IA alone or in combination.展开更多
3-hydroxy-3-methylgulutaryl-coenzyme A （HMG-CoA） reductase inhibitors or statins are a kind of lipid-lowering agents and have been used for the prevention and treatment of Cardiovascular diseases. Recent studies sug...3-hydroxy-3-methylgulutaryl-coenzyme A （HMG-CoA） reductase inhibitors or statins are a kind of lipid-lowering agents and have been used for the prevention and treatment of Cardiovascular diseases. Recent studies suggested that statins, besides lowering cholesterol, may protect vessels by enhancing the activity of endothelial nitric oxide synthase （eNOS）. In the present study, we investigated if simvastatin increases eNOS activity through its phosphorylation in 293 cells （293-eNOS） with stable expression of eNOS. The results showed that incubation of 293-eNOS cells with simvastatin （10 μm/L） for 2 h significantly increased in the activity of eNOS as shown by the conversion of L-arginine to L-citrulline （2889.70±201.51 versus 5630.18＋218.75 pmol/min . mg proteins） （P〈0.01）. Western blotting revealed that simvastatin increased phosphorylation of eNOS at 1177 （ser） and also 495 （thr） but did not affect the overall expression of eNOS or inducible NOS. Further study found that simvastatin raised phosphorylation levels of Akt and AMPK, and such effect could be antagonized by Akt inhibitor or AMPK inhibitor. These results suggest that simvastatin could stimulate,the activity of eNOS via its phosphorylation by Akt and AMPK, which provides a new mechanism, other than lipid-lowering effect, for the cardiovascular protection of statins.展开更多
BACKGROUND: Many studies have showed that apoptosis of endothelial cells plays a curial role in the progress of sepsis. But the role of simvastatin in apoptosis of endothelial cells induced by sepsis is not clear. The...BACKGROUND: Many studies have showed that apoptosis of endothelial cells plays a curial role in the progress of sepsis. But the role of simvastatin in apoptosis of endothelial cells induced by sepsis is not clear. The present study aimed to investigate the role of simvastatin in apoptosis of endothelial cells induced by sepsis and its mechanism.METHODS: Human umbilical vein endothelial cells(HUVECs) were randomly divided into three groups: control group, sepsis serum intervention group(sepsis group) and simvastatin+sepsis serum intervention group(simvastatin group). After 24-hour incubation with corresponding culture medium, the relative growth rate of HUVECS in different groups was detected by MTT assay; the apoptosis of HUVECs was detected by Hoechst33258 assay and fl ow cytometry; and the expression of the Bcl-2 and Bax genes of HUVECs was detected by PCR.RESULTS: Compared with the sepsis group, HUVECs in the simvastatin group had a higher relative growth rate. Apoptotic HUVECs decreased significantly in the simvastatin group in comparison with the sepsis group. Expression of the Bcl-2 gene in HUVECs decreased obviously, but the expression of the Bax gene increased obviously after 24-hour incubation with sepsis serum; however, the expression of the Bcl-2 and Bax genes was just the opposite in the simvastatin group.CONCLUSIONS: Our study suggests that simvastatin can inhibit apoptosis of endothelial cells induced by sepsis through upregulating the expression of Bcl-2 and downregulating Bax. It may be one of the mechanisms for simvastatin to treat sepsis.展开更多
AIMTo determine whether addition of simvastatin could be an important pharmacological rescue therapy for carvedilol non-responders.METHODSOne hundred and two consecutive patients of cirrhosis of liver with significant...AIMTo determine whether addition of simvastatin could be an important pharmacological rescue therapy for carvedilol non-responders.METHODSOne hundred and two consecutive patients of cirrhosis of liver with significant portal hypertension were included.Hepatic venous pressure gradient(HVPG)was measured at the base line and after proper optimization of dose;chronic response was assessed at 3 mo.Carvedilol non-responders were given simvastatin 20 mg per day(increased to 40 mg per day at day 15).Carvedilol plus simvastatin was continued for 1 mo and hemodynamic response was again measured at 1 mo.RESULTSA total of 102 patients with mean age of 58.3±6.6 years were included.Mean baseline HVPG was 16.75±2.12 mmHg and after optimization of dose and reassessment of HVPG at 3 mo,mean reduction of HVPG from baseline was 5.5±1.7 mmHg and 2.8±1.6 mmHg among responders and non-responders respectively(P CONCLUSIONAddition of simvastatin to carvedilol non-responders may prove to be an excellent rescue therapy in patients with portal hypertension.展开更多
A simple, sensitive and specific liquid chromatography-tandem mass spectrometry method was developed for simultaneous quantification of ezetimibe and simvastatin in rat plasma. The deuterium isotopes： ezetimibe d4 an...A simple, sensitive and specific liquid chromatography-tandem mass spectrometry method was developed for simultaneous quantification of ezetimibe and simvastatin in rat plasma. The deuterium isotopes： ezetimibe d4 and simvastatin d6 were used as internal standards for ezetimibe and simvastatin, respectively. MS/MS detection involved a switch of electron spray ionization mode from negative to positive at retention time 3.01 rain. Samples were extracted from plasma by liquid-liquid extraction using tertiary butyl methyl ether. Chromatographic separation was achieved with Agilent Eclipse XBD-CIs column using mobile phase that consisted of a mixture of ammonium acetate （pH4.5; 10 mM）-acetonitrile （25：75 v/v）. The method was linear and validated over the concentration range of 0.2--40.0 ng/rnL for simvastatin and 0.05-15.0 ng/mL for ezetimibe. The transitions selected were m/z 408.3→271.1 and m/z 412.0→275.10 for ezetimibe and ezetimibe d4, and m/z 419.30 → 285.20 and rrdz 425.40 →199.20 for simvastatin and simvastatin d6. Intra- and inter-batch precisions for ezetimibe were 1.6-14.8% and 2.1-13.4%; and for simvastatin 0.94-9.56% and 0.79-12%, respectively. The proposed method was sensitive, selective, precise and accurate for the quantification of ezetimibe and simvastatin simultaneously in rat plasma. The method was successfully applied to a pharmacokinetic study by oral co-administration of ezetimibe and simvastatin in SD rats.展开更多
OBJECTIVE To establish a RP-HPLC method for determination of simvastatin and its related substance lovastatin.METHODS The chromatographic conditions were:a Waters Symmetry Cis column(250 mm×4.6 mm,5 um),a mixture...OBJECTIVE To establish a RP-HPLC method for determination of simvastatin and its related substance lovastatin.METHODS The chromatographic conditions were:a Waters Symmetry Cis column(250 mm×4.6 mm,5 um),a mixture of aceto-nitrile-sodium dihydrogen phosphate(pH 5.4)(65:35)as mobile phase,flow rate 1.0 mL·min^(-1),and detected at 238 nm.RE-SULTS The linear ranges of lovastatin and simvastatin were 0,3~3.0靏穖L^(-1),0.03~0.30 mg·mL^(-1),respectively.The aver-age recovery were 100.2%(RSD=1.5%)and 99.4%(RSD=1.7%),respectively.CONCLUSION The method is simple,quick,sensitive,accurate,and reproducible.It can be used to the quality control of synthetic simvastatin products.展开更多
To observe the effects of simvastatin on nuclear factor kappaB （NF-kB）-DNA binding activity and on the expression of monocyte chemoattractant protein-1 （MCP-1） in atherosclerotic plaque in rabbits and to explore t...To observe the effects of simvastatin on nuclear factor kappaB （NF-kB）-DNA binding activity and on the expression of monocyte chemoattractant protein-1 （MCP-1） in atherosclerotic plaque in rabbits and to explore the anti-atherosclerotic properties beyond its lipid-lowering effects. Thirty-six New Zealand male rabbits were randomly divided into low-cholesterol group （LC）, high- cholesterol group （HC）, high-cholesterol＋ simvastatin group （HC＋S） and then were fed for 12 weeks. At the end of the experiment, standard enzymatic assays, electrophoretic mobility shift as- say （EMSA）, immunohistochemical staining, and morphometry were performed to observe serum lipids, NF-kB-DNA binding activity, MCP-1 protein expression, intirna thickness and plaque area of aorta respectively in all three groups. Our results showed that the serum lipids, NF-kB-DNA binding activity, expression of MCP-1 protein, intima thickness, and plaque area of aorta in the LC and HC＋S groups were significantly lower than those in the HC group （P〈0.05）. There was no significant difference in the serum lipids between the LC and HC＋S groups （P〉0.05）, but the NF-kB-DNA binding activity, the expression of MCP-1 protein and the intirna thickness and plaque area of aorta in the HC＋S group were significantly decreased as compared to the LC group （P〈0. 05）. This study demonstrated that simvastatin could decrease atherosclerosis by inhibiting the NF-kB-DNA binding activity and by reducing the expression of MCP-1 protein.展开更多
Objective::To investigate the neuroprotective effects of simvastatin on lipopolysaccharide(LPS)-indueed rat model of Parkinson's disease(PD) and the mechanisms involved.Methods:Hemiparkinsonian rat models were ind...Objective::To investigate the neuroprotective effects of simvastatin on lipopolysaccharide(LPS)-indueed rat model of Parkinson's disease(PD) and the mechanisms involved.Methods:Hemiparkinsonian rat models were induced by stereotaxieal injection of LPS in the right substantia nigra compacts.After 2 weeks of simvastatin treatment,rotational behavior test was performed after the intraperitoneal injection of apomorphine.Expression of tyroxine hydroxylase(TH) and glial fibrillan acidic protein were analyzed through immunohistochemical staining of substantia nigra and striatum,and the level of TNF-α was evaluated using enzyme-linked immunosorbent assay.Results:Comparing with untreated group,behavioral symptoms of the rats were significantly less in the rats that received simvastatin treatment.The TH positive cell count in substantia nigra and striatum were significantly increased(P<0.05) and TNF- α expression was significantly decreased(P<0.05) in simvastatin group compared to untreated group.Conclusions:Simvastatin could effectively inhibit the activation of astrocytes,reduce TNF-α expression,and exert anti-inflammatory effects,and thus protect the dopaminergic neurons in substantia nigra and striatum of the rat model of PD.展开更多
Objective:To investigate the effect of simvastatin treatment on lipid pr of ile and oxidative stress in hypercholesterolaemic Indian population and determine the effect of simvastatin treatment on the activity of para...Objective:To investigate the effect of simvastatin treatment on lipid pr of ile and oxidative stress in hypercholesterolaemic Indian population and determine the effect of simvastatin treatment on the activity of paraoxonase（PON）.Methods:Analyzed initially before medication administration and four months later after medication.Lipid and lipoprotein measurement were done by enzymatic kits,high density lipoprotein（HDL） was determined by phosphotungstic acid precipitation method and low density lipoprotein（LDL） was calculated by Friedewald’s formula.Lipid peroxidation was measured by three markers namely,conjugated diene,total peroxide,and malondialdehyde.Conjugated diene was assayed by Buege and Aust method.Total peroxide was determined by FOX2 method.Malondialdehyde determination was carried out by Flemming method and total antioxidant status was determined by Ozacan.Paraoxonase activity was determined by measuring the absorbance inrease of p-nitrophenol at 405 nm.Arylesterase activity was calculated from the molar coefficient of 1 310 M<sup>-1</sup> cm<sup>-1</sup>.Results:Simvastatin significantly reduced total cholesterol,triglycerides,LDL,conjugated diene,total peroxide and MDA levels,where as antioxidant status was significantly increased.Besides,simvastatin significantly increased PON1 activity towards paraoxon.Conclusions:The results from the current study indicate simvastatin may have important antioxidant properties via increasing PON activity.展开更多
To evaluate the effectiveness and safety of Taizhi＇an （泰脂安, TZA） capsule combined with Simvastatin （Sim） in treating hyperlipidemia in diabetes mellitus （DM） patients. Methods： Eighty cases of type 2 DM pat...To evaluate the effectiveness and safety of Taizhi＇an （泰脂安, TZA） capsule combined with Simvastatin （Sim） in treating hyperlipidemia in diabetes mellitus （DM） patients. Methods： Eighty cases of type 2 DM patients with hyperlipidemia were randomized into two groups, 40 in each group. The patients in the treated group took orally TZA capsules at the dose of 0.9 g 3 times a day and Sim 10 mg at bedtime. And the patients in the control group were treated with Sim 20 mg alone at bedtime. Both regimens lasted for 12 weeks. Before and after the study the changes of blood lipid levels and adverse reaction were investigated. Results. The serum levels of total cholesterol （TO）, triglycerides （TG） and low density lipoprotein-cholesterol （LDL-C） were decreased respectively by 28.8%, 18.2% and 26.3% in the treated group; and by 29.4%, 19.4% and 24.6% in the control group. On the contrary, high density lipoprotein-cholesterol （HDL-C） was increased by 23.5% in the treated group and by 29.4% in the control group. All these changes were statistically significant before and after treatment （all P〈0.05）, but they did not differ statistically between the two groups （P〉0.05）. There was no significant changes in hemoglobin A1 c （HbA1c）. Patients in the treated group did not develop any adverse reactions. However, ALT was found to be higher above the normal range in 5% of the patients in the control group. Conclusion： In treating hyperlipidemia in DM patients, combination of TZA with Sim 10 mg taken daily achieved satisfactory efficacy which was similar to Sim 20 mg daily alone. But the combination therapy conducted in the treated group proved to be better in safety, and could overcome adverse reactions resulting from Sim that was seen in the control group.展开更多
OBJECTIVE: To investigate the hemostasis effect of spleen-invigorating, Qi-replenishing and blood-arresting formula, on a zebrafish models with simvastatin-induced hemorrhage, and with symptom pattern caused by spleen...OBJECTIVE: To investigate the hemostasis effect of spleen-invigorating, Qi-replenishing and blood-arresting formula, on a zebrafish models with simvastatin-induced hemorrhage, and with symptom pattern caused by spleen failing to control blood, in terms of theory of Traditional Chinese Medicine(TCM).METHODS: In the first experiment, 60 AB strain wild type zebrafishes were randomly assigned into two groups: normal group and model group. The model group was treated with 50 μM simvastatinfor 24 h. The second experiment: The melanin allele mutated Albino strain zebrafishes were divided into normal, model, A group and B group. The observational parameters were as follows: blood flow, velocity of movement, hemorrhage ratio and improvement ratio of hemorrhage.RESULTS: Hemorrhage ratio: in the first experiment, brain hemorrhage ratio was 75%. In the second experiment, heart hemorrhage ratio was 65%.Blood flow: compared with the normal group,there was a significantly decrease in the model group(P < 0.001). Velocity of movement: in the first experimental, compared with the normal group,there was a significantly decrease in the model group(P < 0.001). Improvement ratio of hemorrhage: agents A had little effect in heart hemorrhage of the zebrafish; agents B could reduce heart hemorrhage ratio of the zebrafish, and increase the improvement ratio of hemorrhage.CONCLUSION: The manifestation of zebrafish model with simvastatin-induced hemorrhage is basically similar to that of the clinical symptom pattern caused by spleen's failure to control blood. The Spleen-invigorating, Qi-replenishing and Blood-arresting Formula can reduce the heart hemorrhage ratio of zebrafish induced by simvastatin, and increase the Improvement ratio of hemorrhage.展开更多
Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductases, collectively known as statins, have been shown to minimize cerebral ischemic events in patients. We assessed the mechanisms of simvastatin pretreatment i...Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductases, collectively known as statins, have been shown to minimize cerebral ischemic events in patients. We assessed the mechanisms of simvastatin pretreatment in preventing cerebral ischemia/reperfusion injury in rats using a model of middle cerebral artery occlusion（MCAO）.Rats were pretreated with simvastatin 14 days prior to MCAO induction. At 3, 24, and 48 hours after reperfusion,bradykinin levels in the ischemic penumbra were assayed by ELISA, mRNA levels of bradykinin B2 receptors（BK-2Rs） and CD11b were measured by fluorescent quantitative real-time PCR（RT-PCR）, and co-expression of microglia and BK-2Rs was determined by immunofluorescence. Simvastatin had no effect on bradykinin expression in the ischemic penumbra at any time point. However, the levels of BK-2R and CD11b mRNA in the ischemic penumbra,which were significantly decreased 3 hours after ischemia-reperfusion, were increased in simvastatin-pretreated rats.Moreover, the co-expression of BK-2Rs and microglia was confirmed by immunofluorescence analysis. These results suggest that the beneficial effects of simvastatin pretreatment before cerebral ischemia/reperfusion injury in rats may be partially due to increased expression of BK-2R and CD11b in the ischemic penumbra.展开更多
基金Supported by the Jiangsu Province Key Research and Development Plan(Social Development)Project,No.BE2021611。
文摘BACKGROUND Colorectal cancer(CRC)is a major cause of cancer-related mortality,with limited therapeutic options for advanced stages.Simvastatin,primarily used to lower cholesterol,has shown potential as an anticancer agent.It may exert its effects by inhibiting SERPINE1,a protein implicated in CRC progression,and activating the cyclic guanosine monophosphate-protein kinase G(cGMP/PKG)signaling pathway.Given these findings,this study hypothesizes that simvastatin inhibits CRC cell proliferation and migration by downregulating SERPINE1 and activating the cGMP/PKG pathway,offering a novel therapeutic strategy for CRC management.AIM To study the effects of simvastatin on the function of colon cancer cells and to uncover the underlying mechanisms.METHODS NCM460,HCT-116,and SW620 cell lines were used for in vitro experiments with simvastatin at doses of 20μM,40μM,and 80μM.The Stitch database was used to analyze the target genes of simvastatin,whereas STRING was used to investigate SERPINE1 and its related pathways.HCT-116 and SW620 cells were transfected with single-cell RNA sequencing reveals SERPINE1 with or without Rp-8-Br-cGMP(a PKG inhibitor).Cell toxicity,proliferation,and migration were evaluated using the cell counting kit-8,colony formation,and Transwell assays,respectively.Apoptosis was analyzed via flow cytometry,and levels of reactive oxygen species(ROS),malondialdehyde(MDA),glutathione(GSH),and ferrous ion(Fe^(2+))were detected using commercial kits.Real-time polymerase chain reaction and western blotting were used to analyze gene expression.RESULTS Simvastatin dose-dependently inhibited the proliferation and migration of HCT-116 and SW620 cells while promoting apoptosis.It downregulated Ki-67,proliferating cell nuclear antigen,MMP2,and MMP9,and upregulated Bax,particularly at higher doses.Simvastatin increased the ROS,MDA,and Fe^(2+)levels while decreasing the GSH levels.It downregulated SLC7A11 and ferroportin and upregulated TRF1.SERPINE1 was identified as a core target,with related genes enriched in the cGMP/PKG pathway.SERPINE1 knockdown increased GUCY1B1 and PRKG1 levels,decreased cell viability,and altered oxidative stress markers,with the effects being reversed by Rp-8-Br-cGMP.CONCLUSION Simvastatin effectively inhibited the proliferation and migration of colon cancer cells and promoted apoptosis through the modulation of key targets,such as SERPINE1 and the cGMP/PKG signaling pathway.
基金funded by the Applied Basic Research Foundation of Tianjin(22JCQNJC00230)the Beijing-Tianjin-Hebei Basic Research Cooperation Project(23JCZXJC00050/J230007)the Tianjin Health and Technology Project(TJWJ2024QN056)。
文摘Background:Both simvastatin and metformin have demonstrated potential efficacy in osteoporosis(OP)treatment.However,there is a lack of systematic studies comparing their anti-osteoporotic effects.This study aims to compare the effects of simvastatin and metformin on OP through Mendelian randomization(MR)studies and animal experiments.Methods:Initially,we will analyze the causal impact of simvastatin or metformin treatment on OP prevalence and three common clinical OP diagnostic markers(bone mineral density(BMD),serum osteocalcin(OCN),and tartrate-resistant acid phosphatase(TRAP)levels)using genome-wide association study(GWAS)summary statistics.Additionally,we established animal models to further analyze and compare the anti-osteoporosis effects of simvastatin and metformin.8 male C57BL/6J mice(3-month-old)and 24 male C57BL/6J mice(18-month-old)were treated with simvastatin or metformin for 12 weeks.OP pathology was assessed using histology,immunohistochemistry,biomechanical tests,micro-computed tomography,and osteogenic differentiation assays.Results:In the MR analysis,metformin treatment was significantly associated with lower OP prevalence(OR(95%CI)=0.933(0.902–0.965),β=-0.0694,P<0.001)and higher BMD(OR(95%CI)=3.719(1.750–7.908),β=1.3136,P<0.001).In the animal experiment,both drugs increased bone mass,improved bone microstructure,and promoted osteoblast differentiation.However,metformin appeared more effective in several aspects.It significantly inhibited bone marrow adipocyte and osteoclast differentiation in aged mice compared to simvastatin.Additionally,metformin better promoted the expression of osteoprotegerin(OPG)and collagen type I(Col-I)in bone tissue and maintained the structure and biomechanical properties of cancellous bone.Conclusion:Both drugs significantly preserved bone homeostasis.Particularly,compared with simvastatin,metformin exhibited superior effects in inhibiting adipogenesis,enhancing the OPG/RANKL pathway,and promoting cancellous bone reconstruction.Metformin may serve as a valuable adjunct in preventing and treating OP in the elderly.
基金Research Fund Project of health and Family Planning Commission of Hebei Province(Grant No.20170571)。
文摘The total ginsenosides of ginseng fruit are the main constituents of Zhenyuan capsule,which is mainly used for the treatment of cardiovascular diseases.It has been reported that ginsenoside can affect the activity of CYP450 enzymes.Zhenyuan capsule and simvastatin may interact with each other through CYP3 A4 mediation,then affect the efficacy and even produce adverse reactions.However,no studies have investigated the effects of Zhenyuan capsule on the pharmacokinetics of simvastatin and its active metabolites.In this study,liquid chromatography–electrospray ionization–mass spectrometry(LC-MS/MS)was used to detect the pharmacokinetics of simvastatin and its active metabolites-simvastatin acid with or without Zhenyuan capsule in rats.Compared with the simvastatin alone,the pharmacokinetic parameters of simvastatin and simvastatin acid were significantly different in AUC0–24 and AUC0–∞,and they were decreased in varying degrees(P<0.05).It appeared that the Zhenyuan capsule might increase the activity of CYP3 A4 to some extent.
基金supported by Hebei Social Science Fund Project in 2016(Grant No.HB16LJ006)the Dr. Start-up Fund of North China University of Science and Technology(2015)
文摘Objective:To investigate the preventive and therapeutic effect and mechanism of simvastatin on secondary inflammatory damage of rats with cerebral hemorrhage.Methods:Sixty SD rat aged 9-12 weeks were chosen and divided into the control group,model group and simvastatintreated group randomly with 20 rats in each group.Rats in the model group and simvastatintreated group were infused with autologous fresh uncoagulated blood to the right brain tissue of the basal ganglia to build the cerebral hemorrhage model,while rats in the control group were treated with the same amount of normal saline.Then,rats in the simvastatin-treated group were given a gavage of 3 mg/kg of simvastatin once a day after modeling.Rats in the three groups were given nerve dysfunction score(NDS) and wet-dry weighting method was used to detect the brain water content(BWC) of brain tissues around the lesion of the rats.Then Nissl staining was conducted and the undamaged neurons were counted.Immunohistochemical SP method was applied to count the number of NF-d the immuno fluorκB,TLR4 and IL-1escence method wasβ positive cells in brain tissues around the lesions,an employed to determine the expression levels of NF-κB,TLR4 and IL-1me points were aβ proteins.Results:The NDS results of the simvastatin-treated group at all till significantly higher than those of the model group(P < 0.05);the BWC values of the simvastatin-treated group at all time points were all significantly lower than those of the model group at the same periods(P < 0.05);the number of the undamaged neurons around the lesions of the simvastatin-treated group at all time points were all significantly higher than those of the model group(P < 0.05);seven days after treatment,the number of the NF-κB,TLR4 and IL-1β positive cells in brain tissues around the lesions of the simvastatin-treated group were all significantly lower than those of the model group(P < 0.05),and its expression levels of NF-ower than those of the model group(κB,TLR4 and IL-1P < 0.05).Conclusioβ protein were also significantly lns:Simvastatin can inhibit the expressions of NF-κB,TLR4 and IL-1β proteins in rats with cerebral hemorrhage,and protect neurons and reduce secondary inflammatory damages by down-regulating the above protein-mediated inflammatory responses.
基金supported by grants from the National Nature Science foundation of China(Grant Nos.30872912 and 30830108)
文摘Aim To determine the effect of local simvastatin application on the mRNA expression level of transforming growth factor-β1 （TGF-β1）, bone morphogenetic protein-2 （BMP-2） and vascular endothelial growth factor （VEGF） in the tooth sockets of rat. Methodology Forty-eight male Wistar rats were randomly divided into experimental and control groups （n=24）. Polylactic acid/polyglycolic acid copolymer carriers, with or without simvastatin, were implanted into extraction sockets of right mandibular incisors. The expression of TGF-β1, BMP-2 and VEGF mRNA was determined by in situ hybridization in the tooth extraction socket at five days, one week, two weeks and four weeks after implantation. Results The fusiform stroma cells in the tooth extraction socket began to express TGF-β1, BMP-2 and VEGF mRNA in both experimental and control groups from one week after tooth extraction until the end of experiment. The expression of TGF-131 and BMP-2 mRNA in the experimental group was significantly up-regulated after one, two and four weeks, and expression of VEGF mRNA was significantly increased after one and two weeks compared with that in the control group. Conclusion The findings indicate that local administration of simvastatin can influence alveolar bone remodeling by regulating the expression of a school of growth factors which are crucial to osteogenesis in the tooth extraction socket.
基金supported by the National Natural Science Foundation of China(Nos.81373957,81573567,and 81373919)
文摘Cardiovascular disease(CVD) is the most common cause of death in patients with non-alcoholic fatty liver disease(NAFLD). New therapeutic strategies which have the potential for slowing down the evolution of NAFLD and reducing CVD-related mortality are urgently needed. Statins are well recognized in the treatment of dyslipidemia, but their use in the treatment of NAFLD is limited due to the safety concerns. Ilexgenin A(IA) is one of the main bioactive compounds in ‘Shan-lv-cha', an herbal tea commonly used in China. In the present study, we investigated the possible synergistic therapeutic effects of IA and simvastatin(SV) on NAFLD. IA or SV showed beneficial effects on the rats with NAFLD by lowering the liver weight, liver index and plasma levels of alanine aminotransferase and aspartate aminotransferase, regulating abnormal metabolism of lipids and ameliorating steatosis in liver. IA significantly enhanced the hypolipidemic and anti-inflammation effects of SV. Furthermore, a sensitive, accurate, convenient and reproducible LC-MS method was developed to investigate the effects of IA on the pharmacokinetics of SV. No significant changes were observed in pharmacokinetic parameters of SV and simvastatin hydroxy acid in the IA plus SV co-treated group in comparison with those in the group treated with SV alone. The m RNA levels and activity of CYP3 A1 were not altered by IA. In conclusion, the results obtained from the present study should be helpful for further clinical application of SV and IA alone or in combination.
基金supported by grants from National Natural Sciences Foundation of China (No. 30430320 and 30770882)National 973 Project (No. 2007CB512004)
文摘3-hydroxy-3-methylgulutaryl-coenzyme A （HMG-CoA） reductase inhibitors or statins are a kind of lipid-lowering agents and have been used for the prevention and treatment of Cardiovascular diseases. Recent studies suggested that statins, besides lowering cholesterol, may protect vessels by enhancing the activity of endothelial nitric oxide synthase （eNOS）. In the present study, we investigated if simvastatin increases eNOS activity through its phosphorylation in 293 cells （293-eNOS） with stable expression of eNOS. The results showed that incubation of 293-eNOS cells with simvastatin （10 μm/L） for 2 h significantly increased in the activity of eNOS as shown by the conversion of L-arginine to L-citrulline （2889.70±201.51 versus 5630.18＋218.75 pmol/min . mg proteins） （P〈0.01）. Western blotting revealed that simvastatin increased phosphorylation of eNOS at 1177 （ser） and also 495 （thr） but did not affect the overall expression of eNOS or inducible NOS. Further study found that simvastatin raised phosphorylation levels of Akt and AMPK, and such effect could be antagonized by Akt inhibitor or AMPK inhibitor. These results suggest that simvastatin could stimulate,the activity of eNOS via its phosphorylation by Akt and AMPK, which provides a new mechanism, other than lipid-lowering effect, for the cardiovascular protection of statins.
基金supported by grants from the Medical Research Foundation of Hunan Province(B2013-040)the Science and Technology Development Foundation of Hengyang City(2010kj38)
文摘BACKGROUND: Many studies have showed that apoptosis of endothelial cells plays a curial role in the progress of sepsis. But the role of simvastatin in apoptosis of endothelial cells induced by sepsis is not clear. The present study aimed to investigate the role of simvastatin in apoptosis of endothelial cells induced by sepsis and its mechanism.METHODS: Human umbilical vein endothelial cells(HUVECs) were randomly divided into three groups: control group, sepsis serum intervention group(sepsis group) and simvastatin+sepsis serum intervention group(simvastatin group). After 24-hour incubation with corresponding culture medium, the relative growth rate of HUVECS in different groups was detected by MTT assay; the apoptosis of HUVECs was detected by Hoechst33258 assay and fl ow cytometry; and the expression of the Bcl-2 and Bax genes of HUVECs was detected by PCR.RESULTS: Compared with the sepsis group, HUVECs in the simvastatin group had a higher relative growth rate. Apoptotic HUVECs decreased significantly in the simvastatin group in comparison with the sepsis group. Expression of the Bcl-2 gene in HUVECs decreased obviously, but the expression of the Bax gene increased obviously after 24-hour incubation with sepsis serum; however, the expression of the Bcl-2 and Bax genes was just the opposite in the simvastatin group.CONCLUSIONS: Our study suggests that simvastatin can inhibit apoptosis of endothelial cells induced by sepsis through upregulating the expression of Bcl-2 and downregulating Bax. It may be one of the mechanisms for simvastatin to treat sepsis.
文摘AIMTo determine whether addition of simvastatin could be an important pharmacological rescue therapy for carvedilol non-responders.METHODSOne hundred and two consecutive patients of cirrhosis of liver with significant portal hypertension were included.Hepatic venous pressure gradient(HVPG)was measured at the base line and after proper optimization of dose;chronic response was assessed at 3 mo.Carvedilol non-responders were given simvastatin 20 mg per day(increased to 40 mg per day at day 15).Carvedilol plus simvastatin was continued for 1 mo and hemodynamic response was again measured at 1 mo.RESULTSA total of 102 patients with mean age of 58.3±6.6 years were included.Mean baseline HVPG was 16.75±2.12 mmHg and after optimization of dose and reassessment of HVPG at 3 mo,mean reduction of HVPG from baseline was 5.5±1.7 mmHg and 2.8±1.6 mmHg among responders and non-responders respectively(P CONCLUSIONAddition of simvastatin to carvedilol non-responders may prove to be an excellent rescue therapy in patients with portal hypertension.
文摘A simple, sensitive and specific liquid chromatography-tandem mass spectrometry method was developed for simultaneous quantification of ezetimibe and simvastatin in rat plasma. The deuterium isotopes： ezetimibe d4 and simvastatin d6 were used as internal standards for ezetimibe and simvastatin, respectively. MS/MS detection involved a switch of electron spray ionization mode from negative to positive at retention time 3.01 rain. Samples were extracted from plasma by liquid-liquid extraction using tertiary butyl methyl ether. Chromatographic separation was achieved with Agilent Eclipse XBD-CIs column using mobile phase that consisted of a mixture of ammonium acetate （pH4.5; 10 mM）-acetonitrile （25：75 v/v）. The method was linear and validated over the concentration range of 0.2--40.0 ng/rnL for simvastatin and 0.05-15.0 ng/mL for ezetimibe. The transitions selected were m/z 408.3→271.1 and m/z 412.0→275.10 for ezetimibe and ezetimibe d4, and m/z 419.30 → 285.20 and rrdz 425.40 →199.20 for simvastatin and simvastatin d6. Intra- and inter-batch precisions for ezetimibe were 1.6-14.8% and 2.1-13.4%; and for simvastatin 0.94-9.56% and 0.79-12%, respectively. The proposed method was sensitive, selective, precise and accurate for the quantification of ezetimibe and simvastatin simultaneously in rat plasma. The method was successfully applied to a pharmacokinetic study by oral co-administration of ezetimibe and simvastatin in SD rats.
文摘OBJECTIVE To establish a RP-HPLC method for determination of simvastatin and its related substance lovastatin.METHODS The chromatographic conditions were:a Waters Symmetry Cis column(250 mm×4.6 mm,5 um),a mixture of aceto-nitrile-sodium dihydrogen phosphate(pH 5.4)(65:35)as mobile phase,flow rate 1.0 mL·min^(-1),and detected at 238 nm.RE-SULTS The linear ranges of lovastatin and simvastatin were 0,3~3.0靏穖L^(-1),0.03~0.30 mg·mL^(-1),respectively.The aver-age recovery were 100.2%(RSD=1.5%)and 99.4%(RSD=1.7%),respectively.CONCLUSION The method is simple,quick,sensitive,accurate,and reproducible.It can be used to the quality control of synthetic simvastatin products.
基金This project was supported by a grant from the NationalNatural Sciences Foundation of China (No .30470713)
文摘To observe the effects of simvastatin on nuclear factor kappaB （NF-kB）-DNA binding activity and on the expression of monocyte chemoattractant protein-1 （MCP-1） in atherosclerotic plaque in rabbits and to explore the anti-atherosclerotic properties beyond its lipid-lowering effects. Thirty-six New Zealand male rabbits were randomly divided into low-cholesterol group （LC）, high- cholesterol group （HC）, high-cholesterol＋ simvastatin group （HC＋S） and then were fed for 12 weeks. At the end of the experiment, standard enzymatic assays, electrophoretic mobility shift as- say （EMSA）, immunohistochemical staining, and morphometry were performed to observe serum lipids, NF-kB-DNA binding activity, MCP-1 protein expression, intirna thickness and plaque area of aorta respectively in all three groups. Our results showed that the serum lipids, NF-kB-DNA binding activity, expression of MCP-1 protein, intima thickness, and plaque area of aorta in the LC and HC＋S groups were significantly lower than those in the HC group （P〈0.05）. There was no significant difference in the serum lipids between the LC and HC＋S groups （P〉0.05）, but the NF-kB-DNA binding activity, the expression of MCP-1 protein and the intirna thickness and plaque area of aorta in the HC＋S group were significantly decreased as compared to the LC group （P〈0. 05）. This study demonstrated that simvastatin could decrease atherosclerosis by inhibiting the NF-kB-DNA binding activity and by reducing the expression of MCP-1 protein.
基金supported by Provincial Natural Science Foundation of Hainan(Grant number 811214)Provincial Higher School Scientific Research Project of Hainan(Grant number Hjkj2011-35)was provided by Department of Neurology,Affiliated Hospital of Hainan Medical College
文摘Objective::To investigate the neuroprotective effects of simvastatin on lipopolysaccharide(LPS)-indueed rat model of Parkinson's disease(PD) and the mechanisms involved.Methods:Hemiparkinsonian rat models were induced by stereotaxieal injection of LPS in the right substantia nigra compacts.After 2 weeks of simvastatin treatment,rotational behavior test was performed after the intraperitoneal injection of apomorphine.Expression of tyroxine hydroxylase(TH) and glial fibrillan acidic protein were analyzed through immunohistochemical staining of substantia nigra and striatum,and the level of TNF-α was evaluated using enzyme-linked immunosorbent assay.Results:Comparing with untreated group,behavioral symptoms of the rats were significantly less in the rats that received simvastatin treatment.The TH positive cell count in substantia nigra and striatum were significantly increased(P<0.05) and TNF- α expression was significantly decreased(P<0.05) in simvastatin group compared to untreated group.Conclusions:Simvastatin could effectively inhibit the activation of astrocytes,reduce TNF-α expression,and exert anti-inflammatory effects,and thus protect the dopaminergic neurons in substantia nigra and striatum of the rat model of PD.
文摘Objective:To investigate the effect of simvastatin treatment on lipid pr of ile and oxidative stress in hypercholesterolaemic Indian population and determine the effect of simvastatin treatment on the activity of paraoxonase（PON）.Methods:Analyzed initially before medication administration and four months later after medication.Lipid and lipoprotein measurement were done by enzymatic kits,high density lipoprotein（HDL） was determined by phosphotungstic acid precipitation method and low density lipoprotein（LDL） was calculated by Friedewald’s formula.Lipid peroxidation was measured by three markers namely,conjugated diene,total peroxide,and malondialdehyde.Conjugated diene was assayed by Buege and Aust method.Total peroxide was determined by FOX2 method.Malondialdehyde determination was carried out by Flemming method and total antioxidant status was determined by Ozacan.Paraoxonase activity was determined by measuring the absorbance inrease of p-nitrophenol at 405 nm.Arylesterase activity was calculated from the molar coefficient of 1 310 M<sup>-1</sup> cm<sup>-1</sup>.Results:Simvastatin significantly reduced total cholesterol,triglycerides,LDL,conjugated diene,total peroxide and MDA levels,where as antioxidant status was significantly increased.Besides,simvastatin significantly increased PON1 activity towards paraoxon.Conclusions:The results from the current study indicate simvastatin may have important antioxidant properties via increasing PON activity.
文摘To evaluate the effectiveness and safety of Taizhi＇an （泰脂安, TZA） capsule combined with Simvastatin （Sim） in treating hyperlipidemia in diabetes mellitus （DM） patients. Methods： Eighty cases of type 2 DM patients with hyperlipidemia were randomized into two groups, 40 in each group. The patients in the treated group took orally TZA capsules at the dose of 0.9 g 3 times a day and Sim 10 mg at bedtime. And the patients in the control group were treated with Sim 20 mg alone at bedtime. Both regimens lasted for 12 weeks. Before and after the study the changes of blood lipid levels and adverse reaction were investigated. Results. The serum levels of total cholesterol （TO）, triglycerides （TG） and low density lipoprotein-cholesterol （LDL-C） were decreased respectively by 28.8%, 18.2% and 26.3% in the treated group; and by 29.4%, 19.4% and 24.6% in the control group. On the contrary, high density lipoprotein-cholesterol （HDL-C） was increased by 23.5% in the treated group and by 29.4% in the control group. All these changes were statistically significant before and after treatment （all P〈0.05）, but they did not differ statistically between the two groups （P〉0.05）. There was no significant changes in hemoglobin A1 c （HbA1c）. Patients in the treated group did not develop any adverse reactions. However, ALT was found to be higher above the normal range in 5% of the patients in the control group. Conclusion： In treating hyperlipidemia in DM patients, combination of TZA with Sim 10 mg taken daily achieved satisfactory efficacy which was similar to Sim 20 mg daily alone. But the combination therapy conducted in the treated group proved to be better in safety, and could overcome adverse reactions resulting from Sim that was seen in the control group.
基金Supported by National Program on Key Basic Research Program(973 Program)Project(No.2013CB531705)--Study on the Visceral Picture Theory of "Spleen Governs Transportation and Transformation-controls blood"
文摘OBJECTIVE: To investigate the hemostasis effect of spleen-invigorating, Qi-replenishing and blood-arresting formula, on a zebrafish models with simvastatin-induced hemorrhage, and with symptom pattern caused by spleen failing to control blood, in terms of theory of Traditional Chinese Medicine(TCM).METHODS: In the first experiment, 60 AB strain wild type zebrafishes were randomly assigned into two groups: normal group and model group. The model group was treated with 50 μM simvastatinfor 24 h. The second experiment: The melanin allele mutated Albino strain zebrafishes were divided into normal, model, A group and B group. The observational parameters were as follows: blood flow, velocity of movement, hemorrhage ratio and improvement ratio of hemorrhage.RESULTS: Hemorrhage ratio: in the first experiment, brain hemorrhage ratio was 75%. In the second experiment, heart hemorrhage ratio was 65%.Blood flow: compared with the normal group,there was a significantly decrease in the model group(P < 0.001). Velocity of movement: in the first experimental, compared with the normal group,there was a significantly decrease in the model group(P < 0.001). Improvement ratio of hemorrhage: agents A had little effect in heart hemorrhage of the zebrafish; agents B could reduce heart hemorrhage ratio of the zebrafish, and increase the improvement ratio of hemorrhage.CONCLUSION: The manifestation of zebrafish model with simvastatin-induced hemorrhage is basically similar to that of the clinical symptom pattern caused by spleen's failure to control blood. The Spleen-invigorating, Qi-replenishing and Blood-arresting Formula can reduce the heart hemorrhage ratio of zebrafish induced by simvastatin, and increase the Improvement ratio of hemorrhage.
文摘Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductases, collectively known as statins, have been shown to minimize cerebral ischemic events in patients. We assessed the mechanisms of simvastatin pretreatment in preventing cerebral ischemia/reperfusion injury in rats using a model of middle cerebral artery occlusion（MCAO）.Rats were pretreated with simvastatin 14 days prior to MCAO induction. At 3, 24, and 48 hours after reperfusion,bradykinin levels in the ischemic penumbra were assayed by ELISA, mRNA levels of bradykinin B2 receptors（BK-2Rs） and CD11b were measured by fluorescent quantitative real-time PCR（RT-PCR）, and co-expression of microglia and BK-2Rs was determined by immunofluorescence. Simvastatin had no effect on bradykinin expression in the ischemic penumbra at any time point. However, the levels of BK-2R and CD11b mRNA in the ischemic penumbra,which were significantly decreased 3 hours after ischemia-reperfusion, were increased in simvastatin-pretreated rats.Moreover, the co-expression of BK-2Rs and microglia was confirmed by immunofluorescence analysis. These results suggest that the beneficial effects of simvastatin pretreatment before cerebral ischemia/reperfusion injury in rats may be partially due to increased expression of BK-2R and CD11b in the ischemic penumbra.
