Chemotherapy-induced intestinal mucositis(IM)is a prevalent complication affecting up to 80%of cancer patients undergoing treatment.Current therapies focus on symptomatic relief rather than addressing the underlying m...Chemotherapy-induced intestinal mucositis(IM)is a prevalent complication affecting up to 80%of cancer patients undergoing treatment.Current therapies focus on symptomatic relief rather than addressing the underlying mechanism.Recent advances in integrative medicine highlight the potential of traditional Chinese medicine formulations as alternatives or adjuncts to existing therapies.In this context,this editorial discusses the recent results of a study published by Qiu et al,which investigates the multifaceted potential of modified Pulsatilla decoction(PD),a formulation of PD with licorice(Glycyrrhiza uralensis)and Ejiao(Colla corii asini),on 5-fluorouracil-induced IM in mice to alleviate clinical symptoms including diarrhea,weight loss,and intestinal damage.A series of histological,biochemical,bioinformatic,and microbiological assays evaluated body weight,diarrhea scores,inflammatory cytokine profiles,oxidative stress modulation,and microbiota composition.The findings indicated a reduction in diarrhea and oxidative stress,as well as an improvement in body weight and intestinal histopathology.Furthermore,the modified PD suppressed the TLR4/MyD88/nuclear factor kappa-B inflammatory pathway and down-regulated key proinflammatory cytokines.Moreover,the study underscores the role of gut microbiota in IM pathogenesis.Modified PD treatment reshaped microbial diversity by promoting beneficial genera such as Bacteroides acidifaciens while suppressing pathogenic species like Salmonella.These findings suggest that the therapeutic effects of the modified PD extend beyond inflammation modulation to encompass microbiome reprogramming and mucosal barrier repair.Although the study provides significant insights,several limitations still prevail.The broader implications of modified PD in gastrointestinal disorders and integrative oncology need further exploration.展开更多
BACKGROUND Modified Pulsatilla decoction(PD),a PD with licorice and ejiao,is a classic Traditional Chinese Medicine formula with significant efficacy in treating intestinal mucositis(IM)induced by tumor therapy.Howeve...BACKGROUND Modified Pulsatilla decoction(PD),a PD with licorice and ejiao,is a classic Traditional Chinese Medicine formula with significant efficacy in treating intestinal mucositis(IM)induced by tumor therapy.However,its specific molecular and biological mechanisms remain unclear.AIM To investigate the therapeutic effect and mechanism of modified PD in IM.METHODS This study used an IM mouse model established using 5-fluorouracil injections to investigate the effects of the modified PD(3,6,and 12 g/kg)in IM.The primary chemical components of the modified PD were identified using liquid chromatography-mass spectrometry.Body weight loss,diarrhea scores,intestinal length,histopathological scores,and inflammatory cytokine levels were measured to evaluate the effects of the modified PD in IM.Effects on the TLR4/MyD88/NF-κB pathway were evaluated using western blot analysis.The intestinal microbiota was characterized using Illumina NovaSeq sequencing.RESULTS The results showed that modified PD significantly improved weight loss and diarrhea and shortened the intestines in IM mice.Mechanistically,modified PD suppressed the TLR4/MyD88/NF-κB pathway and downregulated the expression of reactive oxygen species,lipopolysaccharides,and pro-inflammatory cytokines(IL-1β,TNF-α,IFN-γ,IL-6,IL-8,and IL-17),while increasing the expression of the anti-inflammatory cytokine IL-10.Furthermore,modified PD protected the intestinal mucosal barrier by increasing the expression of tight junction proteins(occludin-1,claudin-1,and ZO-1)and mucin-2.Finally,16S rDNA sequencing revealed that modified PD improved intestinal dysbiosis.CONCLUSION Our research offers new insights into the potential mechanism of modified PD in alleviating IM and provides experimental evidence supporting its pharmaceutical application in clinical IM treatment.展开更多
Objective:The present study investigated how mild moxibustion treatment affects the intestinal Microbiome and expression of NLRP3-related immune factors in a rat model of intestinal mucositis(IM)induced with 5-fluorou...Objective:The present study investigated how mild moxibustion treatment affects the intestinal Microbiome and expression of NLRP3-related immune factors in a rat model of intestinal mucositis(IM)induced with 5-fluorouracil(5-Fu).Methods:Forty male Sprague-Dawley rats were randomly divided into control,chemotherapy,moxibustion and probiotics groups.The IM rat model was established by intraperitoneal injection of 5-Fu.Mild moxibustion treatment and intragastric probiotic administration were provided once daily for 15 days.Tissue morphology,serum levels of inflammatory factors and the expression levels of tight junction proteins,caspase-1,gasdermin D and NLRP3 were evaluated in colon tissue,through hematoxylin and eosin staining,electron microscopy,enzyme-linked immunosorbent assay,Western blotting,quantitative realtime reverse transcription polymerase chain reaction and immunofluorescence.Gut microbiome profiling was conducted through 16 S rRNA amplicon sequencing.Results:Moxibustion and probiotic treatments significantly increased the expression levels of tight junction proteins,reduced cell apoptosis and the expression levels of caspase-1,gasdermin D and NLRP3;they also decreased the serum levels of tumor necrosis factor-α,interleukin(IL)-6,IL-1βand IL-18,while increasing serum levels of IL-10.Moxibustion and probiotic treatments also corrected the reduction inα-diversity andβ-diversity in IM rats,greatly increased the proportion of the dominant bacterial genus Lactobacillus and reduced the abundance of the genera Roseburia and Escherichia in chemotherapytreated rats to levels observed in healthy animals.We also found that these dominant genera were firmly correlated with the regulation of pyroptosis-associated proteins and inflammatory factors.Finally,moxibustion and probiotic treatments elicited similar effects in regulating intestinal host-microbial homeostasis and the expression of NLRP3 inflammasome-related factors.Conclusion:Moxibustion exerts its therapeutic effect on IM by ameliorating mucosal damage and reducing inflammation.Moreover,moxibustion modulates the gut microbiota,likely via decreasing the expression levels of the NLRP3 inflammasome.展开更多
BACKGROUND Radiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients.However,they can also damage normal cells and cause serious intestinal toxicity,leading to gastrointestina...BACKGROUND Radiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients.However,they can also damage normal cells and cause serious intestinal toxicity,leading to gastrointestinal mucositis[1].Traditional Chinese medicine is effective in improving the side effects of chemotherapy.Wumei pills(WMP)was originally documented in the Treatise on Exogenous Febrile Diseases.It has a significant effect on chronic diarrhea and other gastrointestinal diseases,but it is not clear whether it affects chemotherapy induced intestinal mucositis(CIM).AIM To explore the potential mechanism of WMP in the treatment of CIM through experimental research.METHODS We used an intraperitoneal injection of 5-fluorouracil(5-Fu)to establish a CIM mouse model and an oral gavage of WMP decoction(11325 and 22650 mg/kg)to evaluate the efficacy of WMP in CIM.We evaluated the effect of WMP on CIM by observing the general conditions of the mice(body weight,food intake,spleen weight,diarrhea score,and hematoxylin and eosin stained tissues).The expression of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β,and myeloperoxidase(MPO),as well as the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB(TLR4/MyD88/NF-κB)signaling pathway proteins and tight junction proteins(zonula occludens-1,claudin-1,E-cadherin,and mucin-2)was determined.Furthermore,intestinal permeability,intestinal flora,and the levels of short-chain fatty acids(SCFA)were also assessed.RESULTS WMP effectively improved the body weight,spleen weight,food intake,diarrhea score,and inflammatory status of the mice with intestinal mucositis,which preliminarily confirmed the efficacy of WMP in CIM.Further experiments showed that in addition to reducing the levels of TNF-α,IL-1β,IL-6,and MPO and inhibiting the expression of the TLR4/MyD88/NF-κB pathway proteins,WMP also repaired the integrity of the mucosal barrier of mice,regulated the intestinal flora,and increased the levels of SCFA(such as butyric acid).CONCLUSION WMP can play a therapeutic role in CIM by alleviating inflammation,restoring the mucosal barrier,and regulating gut microbiota.展开更多
Restoring the balance of gut microbiota has emerged as a critical strategy in treating intestinal disorders,with probiotics playing a pivotal role in maintaining bacterial equilibrium.Surgical preparations,trauma,and ...Restoring the balance of gut microbiota has emerged as a critical strategy in treating intestinal disorders,with probiotics playing a pivotal role in maintaining bacterial equilibrium.Surgical preparations,trauma,and digestive tract reconstruction associated with intestinal surgeries often disrupt the intestinal flora,prompting interest in the potential role of probiotics in postoperative recovery.Lan et al conducted a prospective randomized study on 60 patients with acute appendicitis,revealing that postoperative administration of Bacillus licheniformis capsules facilitated early resolution of inflammation and restoration of gastrointestinal motility,offering a novel therapeutic avenue for accelerated postoperative recovery.This editorial delves into the effects of perioperative probiotic supplementation on physical and intestinal recovery following surgery.Within the framework of enhanced recovery after surgery,the exploration of new probiotic supplementation strategies to mitigate surgical complications and reshape gut microbiota is particularly intriguing.展开更多
The intestinal mucosa is the intestinal lumen tissue that protects the intestine from invasion,maintains intestinal barrier function,and participates in the immune response.Diseases such as inflammatory enteritis and ...The intestinal mucosa is the intestinal lumen tissue that protects the intestine from invasion,maintains intestinal barrier function,and participates in the immune response.Diseases such as inflammatory enteritis and intestinal infections can cause damage to the intestinal mucosal barrier and dysfunction.The aim of this study was to investigate the improvement mechanism of malvidin-3-O-galactoside(M3G)on small intestinal mucosal barrier function.C57BL/6J male mice were given dextran sodium sulfate(DSS)for 7 days to induce enteritis,and then were fed normally with or without M3G supplementation for another 7 days.The results showed that M3G supplementation significantly improved the disease activity index(DAI)score and small intestinal tissue injury in mice with DSS induced enteritis.M3G ameliorated the small intestinal mucosal mechanical barrier function by modulating the expression of mucin 2(MUC2),zona occludens 1(ZO-1),Occludin,Claudin-1,intestinal fatty acid binding protein(iFABP),and trefoil factor 3(TFF3)in the small intestine mucosa,and the serum levels of D-lactic acid(D-LA),lipopolysaccharide(LPS),and diamine oxidase(DAO)were significantly decreased.Additionally,M3G also relieved the small intestinal immunologic barrier of mice by decreasing the immune protein levels of immunoglobulin A(IgA),immunoglobulin M(IgM),and immunoglobulin G(IgG)in serum,and secretory immunoglobulin A(SIgA)level in small intestine tissue.Furthermore,M3G inhibited the expression of Notch pathway-related proteins such as Notch1,Notch intracellular domain(NICD),delta-like ligand 4(DLL4),delta-like ligand 1(DLL1),and hairy/enhancer of split 1(Hes1).In conclusion,the results demonstrated that M3G can improve intestinal mucosal barrier function by inhibiting Notch pathway.展开更多
The intestinal mucosal barrier serves as a vital guardian of the gut health,maintaining a delicate equilibrium between gut microbiota and host immune homeostasis.Gasdermin D(GSDMD),a key executioner of pyroptosis down...The intestinal mucosal barrier serves as a vital guardian of the gut health,maintaining a delicate equilibrium between gut microbiota and host immune homeostasis.Gasdermin D(GSDMD),a key executioner of pyroptosis downstream of the inflammasome,has been found to play intricate roles in modulating colitis by influencing intestinal macrophages and regulating mucus secretion from goblet cells.However,the exact nature of the regulatory function of GSDMD in maintaining intestinal immune homeostasis and defending against pathogens remains to be elucidated.In the current study,by using the Citrobacter rodentium infection model,we found that GSDMD played a key role in the defense against intestinal Citrobacter rodentium infection,with high expression levels in intestinal epithelial and lamina propria myeloid cells.Our results showed that GSDMD acted specifically in intestinal epithelial cells to combat the infection,independently of its effects on antimicrobial peptides or mucin secretion.Instead,the resistance was mediated by the N-terminal fragment of GSDMD,highlighting its importance in intestinal immunity.However,the specific mechanism underlying the N-terminal activity of GSDMD in protecting against intestinal bacterial infections requires future investigation.展开更多
OBJECTIVE: To investigate the mechanism and effect of Renshen(Radix Ginseng) polysaccharide on the migration of intestinal epithelial cell line 6(IEC-6), as well as the repair mechanism of Renshen(Radix Ginseng) polys...OBJECTIVE: To investigate the mechanism and effect of Renshen(Radix Ginseng) polysaccharide on the migration of intestinal epithelial cell line 6(IEC-6), as well as the repair mechanism of Renshen(Radix Ginseng) polysaccharide on colonic injury induced by dextran sulfate sodium(DSS) in mice. METHODS: Mice were fed 3%(w/v) DSS for 6 d to create colonic lesions. A cell-migration model was created using cell scratching. m RNA expression, protein expression, translation efficiency of m RNA, and nucleoplasmic distribution of human antigen R(Hu R) were determined by real-time reverse transcription-quantitative polymerase chain reaction, western blotting, a dual luciferase reporter system, and immunofluorescence staining, respectively. RESULTS: Renshen(Radix Ginseng) polysaccharide promoted the migration of IEC-6 cells and affected expression of stromal interaction molecule 1(STIM1) and cell division cycle 42(Cdc42) at transcriptional and posttranscriptional levels. CONCLUSIONS: Renshen(Radix Ginseng) polysaccharideinduced repair of intestinal mucosal injury may be mediated by increased cell migration via polyaminebased regulatory mechanisms. In vitro and in vivo experiments suggest that Renshen(Radix Ginseng) polysaccharide-induced post-transcriptional regulation of STIM1 and Cdc42 may be related to differences in the regulation of different target genes by Hu R. Taken together, these data provide a reference for further exploration of the protective effect of Renshen(Radix Ginseng) on the intestinal mucosa.展开更多
BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology.Alkaline sphingomyelinase(alk-SMase)is specifically expressed by intestinal epithelial cells,and has been reported ...BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology.Alkaline sphingomyelinase(alk-SMase)is specifically expressed by intestinal epithelial cells,and has been reported to play an anti-inflammatory role.However,the underlying mechanism is still unclear.AIM To explore the mechanism of alk-SMase anti-inflammatory effects on intestinal barrier function and oxidative stress in dextran sulfate sodium(DSS)-induced colitis.METHODS Mice were administered 3%DSS drinking water,and disease activity index was determined to evaluate the status of colitis.Intestinal permeability was evaluated by gavage administration of fluorescein isothiocyanate dextran,and bacterial translocation was evaluated by measuring serum lipopolysaccharide.Intestinal epithelial cell ultrastructure was observed by electron microscopy.Western blotting and quantitative real-time reverse transcription-polymerase chain reaction were used to detect the expression of intestinal barrier proteins and mRNA,respectively.Serum oxidant and antioxidant marker levels were analyzed using commercial kits to assess oxidative stress levels.RESULTS Compared to wild-type(WT)mice,inflammation and intestinal permeability in alk-SMase knockout(KO)mice were more severe beginning 4 d after DSS induction.The mRNA and protein levels of intestinal barrier proteins,including zonula occludens-1,occludin,claudin-3,claudin-5,claudin-8,mucin 2,and secretory immunoglobulin A,were significantly reduced on 4 d after DSS treatment.Ultrastructural observations revealed progressive damage to the tight junctions of intestinal epithelial cells.Furthermore,by day 4,mitochondria appeared swollen and degenerated.Additionally,compared to WT mice,serum malondialdehyde levels in KO mice were higher,and the antioxidant capacity was significantly lower.The expression of the transcription factor nuclear factor erythroid 2-related factor 2(Nrf2)in the colonic mucosal tissue of KO mice was significantly decreased after DSS treatment.mRNA levels of Nrf2-regulated downstream antioxidant enzymes were also decreased.Finally,colitis in KO mice could be effectively relieved by the injection of tertiary butylhydroquinone,which is an Nrf2 activator.CONCLUSION Alk-SMase regulates the stability of the intestinal mucosal barrier and enhances antioxidant activity through the Nrf2 signaling pathway.展开更多
Background:The aim of this study was to investigate the effects of different minimally invasive surgical procedures on intestinal muco-sal barrier function.Methods:In this study,76 patients who underwent minimally inv...Background:The aim of this study was to investigate the effects of different minimally invasive surgical procedures on intestinal muco-sal barrier function.Methods:In this study,76 patients who underwent minimally invasive gastric cancer surgery were selected,and peripheral blood was collected to test the levels of serum plasma D-lactic acid,diamine oxidase,and bacterial endotoxin before and 1 and 3 days after sur-gery.These markers were compared at different time points before and after surgery to understand the recovery of the intestinal muco-sal barrier function in patients after surgery.Results:On the first postoperative day,the change in serum D-lactic acid relative to the preoperative levels was significantly(P<0.05)lower in the laparoscopic surgery group(4.05[-0.195,6.917 mmol/L])than in the robot-assisted surgery group(7.56[5.190,12.145 mmol/L]).Both the serum D-lactic acid and bacterial endotoxin levels were significantly higher on the first postoperative day compared with preoperative levels,and although they showed a gradual decrease by the third day,they remained significantly higher than the pre-operative levels(P<0.05).The Student-Newman-Keuls method for pairwise comparison of the measurements at each time point dem-onstrated that the differences in D-lactic acid and bacterial endotoxin levels between the preoperative sample and the sample collected on the third postoperative day were statistically significant(P<0.05).Conclusions:Compared with the laparoscopic surgery group,the robotic surgery group showed larger changes in the postoperative serum D-lactic acid level,suggesting that the robotic surgery resulted in greater damage to the barrier function of the intestinal mucosa.The serum D-lactic acid and bacterial endotoxin levels were significantly higher in postoperative patients and showed a trend to gradually decrease,suggesting that the intestinal mucosal barrier function of patients after minimally invasive gastric cancer surgery is damaged and then gradually recovers.展开更多
Ulcerative colitis(UC)is a chronic inflammatory bowel diseasethat significantly affects the quality of life of patients.Traditional treatments often have limitations,and alternative therapies are being explored.Miao M...Ulcerative colitis(UC)is a chronic inflammatory bowel diseasethat significantly affects the quality of life of patients.Traditional treatments often have limitations,and alternative therapies are being explored.Miao Medicine,particularly Jinlong Zhi Xie Fang Enema,is a traditional herbal remedy used to treat UC symptoms,especially in patients with Large Intestine Damp-Heat Syndrome.However,clinical evidence supporting its efficacy is limited.展开更多
The incidence rate and harmfulness of depression are increasing yearly,and the research on the antidepressant effect of regulating the intestinal microecology balance has attracted widespread attention.The purpose of ...The incidence rate and harmfulness of depression are increasing yearly,and the research on the antidepressant effect of regulating the intestinal microecology balance has attracted widespread attention.The purpose of this research was to study the preventive effects and the regulatory mechanism of edible Lilium-egg yolk compound powder(BHT)on gut-brain crosstalk in depressive rats induced by chronic unpredictable mild stress(CUMS)through the“microbiota-gut-brain”axis.Results showed that infusion of BHT for 21 days ameliorated the morphology of the hippocampus and colon,increased the rate of sucrose preference,reduced the immobility time of forced swimming,increased the expression level of anti-inflammatory cytokine interleukin(IL)-10 in serum,up-regulated the expression level of plasma neurotransmitter 5-hydroxytryptamine(5-HT),downregulated the expression of inflammatory factors tumor necrosis factor-α(TNF-α),IL-6,and IL-1βand neurotransmitter glutamic acid(Glu)in serum,and decreased the expression levels of lipopolysaccharide(LPS),diamine oxidase(DAO)and lactate dehydrogenase(LD)in plasma.The underlying mechanism may be to reduce the activation of microglia(lower levels of CD11 antigen-like family member B(CD11b),ionized calcium binding adaptor molecule 1(Iba1)protein and gene expression),regulate hippocampal glucocorticoid receptor/brain-derived neurotrophic factor/neuropeptide Y(GR/BDNF/NPY)signaling pathway(higher levels of GR,BDNF,NPY protein and gene expression),enhance intestinal mucosal barrier function(higher levels of ZO-1,occludin protein and gene expression),regulate the composition and structure of intestinal flora(analysis results of linear discriminant analysis effect size(LEf Se)combined with random forest showed that Prevotella and Paraprevotella might be biomarkers of BHT intervention in depression),and it is related to the improvement of glutathione metabolism,and other metabolic pathways.Pearson correlation analysis found that 5-HT is strongly positively correlated with Prevotella,and Glu has a strong negative correlation with Prevotella.In conclusion,BHT can exert its antidepressant effect on CUMS-induced rats through microbiota-gut-brain interaction,can be used as an alternative to food recuperation for human depression.展开更多
BACKGROUND Hepatic fibrosis(HF)represents a pivotal stage in the progression and potential reversal of cirrhosis,underscoring the importance of early identification and therapeutic intervention to modulate disease tra...BACKGROUND Hepatic fibrosis(HF)represents a pivotal stage in the progression and potential reversal of cirrhosis,underscoring the importance of early identification and therapeutic intervention to modulate disease trajectory.AIM To explore the complex relationship between chronic hepatitis B(CHB)-related HF and gut microbiota to identify microbiota signatures significantly associated with HF progression in CHB patients using advanced machine learning algorithms.METHODS This study included patients diagnosed with CHB and classified them into HF and non-HF groups based on liver stiffness measurements.The HF group was further subdivided into four subgroups:F1,F2,F3,and F4.Data on clinical indicators were collected.Stool samples were collected for 16S rRNA sequencing to assess the gut microbiome.Microbiota diversity,relative abundance,and linear discriminant analysis effect size(LEfSe)were analyzed in different groups.Correlation analysis between clinical indicators and the relative abundance of gut microbiota was performed.The random forest and eXtreme gradient boosting algorithms were used to identify key differential gut microbiota.The Shapley additive explanations were used to evaluate microbiota importance.RESULTS Integrating the results from univariate analysis,LEfSe,and machine learning,we identified that the presence of Dorea in gut microbiota may be a key feature associated with CHB-related HF.Dorea possibly serves as a core differential feature of the gut microbiota that distinguishes HF from non-HF patients,and the presence of Dorea shows significant variations across different stages of HF(P<0.05).The relative abundance of Dorea significantly decreases with increasing HF severity(P=0.041).Moreover,the gut microbiota composition in patients with different stages of HF was found to correlate with several liver function indicators,such asγ-glutamyl transferase,alkaline phosphatase,total bilirubin,and the aspartate aminotransferase/alanine transaminase ratio(P<0.05).The associated pathways were predominantly enriched in biosynthesis,degradation/utilization/assimilation,generation of precursors,metabolites,and energy,among other categories.CONCLUSION HF affects the composition of the gut microbiota,indicating that the gut microbiota plays a crucial role in its pathophysiological processes.The abundance of Dorea varies significantly across various stages of HF,making it a potential microbial marker for identifying HF onset and progression.展开更多
BACKGROUND： The gut is capable of inducing multiple organ dysfunction syndrome （MODS）. In the diagnosis and treatment of critical ill patients, doctors should pay particular attention to the protection or recovery ...BACKGROUND： The gut is capable of inducing multiple organ dysfunction syndrome （MODS）. In the diagnosis and treatment of critical ill patients, doctors should pay particular attention to the protection or recovery of intestinal barrier function. However, no reliable diagnostic criteria are available clinically. This study aimed to assess the changes of intestinal mucosal barrier function in surgically critical ill patients as well as their signi？ cance.METHODS： Thirty-eight surgically critical ill patients were enrolled as a study group （APACHE II〉8 scores）, and 15 non-critical ill patients without intestinal dysfunction were selected as a control group （APACHE II〈6）. General information, symptoms, physical signs, and APACHE II scores of the patients were recorded. The patients in the study group were subdivided into an intestinal dysfunction group （n=26） and a non-intestinal dysfunction group （n=12）. Three ml venous blood was collected from the control group on admission and the same volume of plasma was collected from the study group both on admission and in the period of recovery. The plasma concentrations of endotoxin, diamine oxidase （DAO）, D-lactate, and intestinal fatty-acid binding protein （iFABP） were detected respectively. The data collected were analyzed by the SPSS 17.0 software for Windows. RESULTS： The levels of variables were significantly higher in the study group than in the control group （P〈0.01）. They were higher in the intestinal dysfunction group than in the non-intestinal dysfunction group （DAO P〈0.05, endotoxin, D-lactate, iFABP P〈0.01）. In the non-intestinal dysfunction group compared with the control group, the level of endotoxin was not significant （P〉0.05）, but the levels of DAO, D-lactate and iFABP were statistically significant （P〈0.05）. The levels of variables in acute stage were higher than those in recovery stage （P〈0.01）.The death group showed higher levels of variables than the survival group （endotoxin and D-lactate P〈0.01, DAO and iFABP P〈0.05）.CONCLUSION： The plasma concentrations of endotoxin, DAO, D-lactate, and intestinal fatty-acid binding protein （iFABP） could re？ ect a better function of the intestinal mucosa barrier in surgically critical ill patients.展开更多
Intestinal microecology is the main component of human microecology.Intestinal microecology consists of intestinal microbiota,intestinal epithelial cells,and intestinal mucosal immune system.These components are inter...Intestinal microecology is the main component of human microecology.Intestinal microecology consists of intestinal microbiota,intestinal epithelial cells,and intestinal mucosal immune system.These components are interdependent and establish a complex interaction network that restricts each other.According to the impact on the human body,there are three categories of symbiotic bacteria,opportunistic pathogens,and pathogenic bacteria.The intestinal microecology participates in digestion and absorption,and material metabolism,and inhibits the growth of pathogenic microorganisms.It also acts as the body’s natural immune barrier,regulates the innate immunity of the intestine,controls the mucosal barrier function,and also participates in the intestinal epithelial cells’physiological activities such as hyperplasia or apoptosis.When the steady-state balance of the intestinal microecology is disturbed,the existing core intestinal microbiota network changes and leads to obesity,diabetes,and many other diseases,especially irritable bowel syndrome,inflammatory bowel disease(IBD),and colorectal malignancy.Intestinal diseases,including tumors,are particularly closely related to intestinal microecology.This article systematically discusses the research progress on the relationship between IBD and intestinal microecology from the pathogenesis,treatment methods of IBD,and the changes in intestinal microbiota.展开更多
AIM:To study whether over-starvation aggravates intestinal mucosal injury and promotes bacterial and endotoxin translocation in a high-altitude hypoxic environment.METHODS:Sprague-Dawley rats were exposed to hy-pobari...AIM:To study whether over-starvation aggravates intestinal mucosal injury and promotes bacterial and endotoxin translocation in a high-altitude hypoxic environment.METHODS:Sprague-Dawley rats were exposed to hy-pobaric hypoxia at a simulated altitude of 7000 m for 72 h.Lanthanum nitrate was used as a tracer to detect intestinal injury.Epithelial apoptosis was observed with terminal deoxynucleotidyl transferase dUTP nick end labeling staining.Serum levels of diamino oxidase(DAO),malondialdehyde(MDA),glutamine(Gln),superoxide dismutase(SOD) and endotoxin were measured in intestinal mucosa.Bacterial translocation was detected in blood culture and intestinal homogenates.In addition,rats were given Gln intragastrically to observe its protective effect on intestinal injury.RESULTS:Apoptotic epithelial cells,exfoliated villi and inflammatory cells in intestine were increased with edema in the lamina propria accompanying effusion of red blood cells.Lanthanum particles were found in the intercellular space and intracellular compartment.Bacterial translocation to mesenteric lymph nodes(MLN) and spleen was evident.The serum endotoxin,DAO and MDA levels were significantly higher while the serum SOD,DAO and Gln levels were lower in intestine(P< 0.05).The bacterial translocation number was lower in the high altitude hypoxic group than in the high altitude starvation group(0.47±0.83 vs 2.38±1.45,P<0.05).The bacterial translocation was found in each organ,especially in MLN and spleen but not in peripheral blood.The bacterial and endotoxin translocations were both markedly improved in rats after treatment with Gln.CONCLUSION:High-altitude hypoxia and starvation cause severe intestinal mucosal injury and increase bacterial and endotoxin translocation,which can be treated with Gln.展开更多
BACKGROUND Intestinal mucosal barrier injury and gastrointestinal dysfunction are important causes of sepsis.However,few studies have investigated the effects of enteral underfeeding on gastrointestinal function in se...BACKGROUND Intestinal mucosal barrier injury and gastrointestinal dysfunction are important causes of sepsis.However,few studies have investigated the effects of enteral underfeeding on gastrointestinal function in sepsis.Moreover,no consensus on goal enteral caloric intake has been reached in sepsis.AIM To investigate the effects of different goal caloric requirements of enteral nutrition on the gastrointestinal function and outcomes in the acute phase of sepsis.METHODS Patients were randomly assigned to receive 30%(defined as group A),60%(group B),or 100%(group C)of goal caloric requirements of enteral nutrition in this prospective pilot clinical trial.The acute gastrointestinal injury(AGI)grades,incidence of feeding intolerance(FI),daily caloric intake,nutritional and inflammatory markers,and biomarkers of mucosal barrier function were collected during the first 7 d of enteral feeding.The clinical severity and outcome variables were also recorded.RESULTS A total of 54 septic patients were enrolled.The days to goal calorie of group C(2.55±0.82)were significantly longer than those of group A(3.50±1.51;P=0.046)or B(4.85±1.68;P<0.001).The FI incidence of group C(16.5%)was higher than that of group A(5.0%)or B(8.7%)(P=0.009).No difference in the incidence of FI symptoms was found between groups A and B.The serum levels of barrier function biomarkers of group B were significantly lower than those of group A(P<0.05)on the 7th day of feeding.The prealbumin and IL-6 levels of group A were lower than those of group B(P<0.05)on the 7th day of feeding.No significant differences in the clinical outcome variables or 28-d mortality were found among the three groups.CONCLUSION Early moderate enteral underfeeding(60%of goal requirements)could improve the intestinal barrier function and nutritional and inflammatory status without increasing the incidence of FI symptoms in sepsis.However,further large-scale prospective clinical trials and animal studies are required to test our findings.Moreover,the effects of different protein intake on gastrointestinal function and outcomes should also be investigated in future work.展开更多
BACKGROUND Intestinal mucosal barrier dysfunction plays an important role in the pathogenesis of ulcerative colitis(UC).Recent studies have revealed that impaired autophagy is associated with intestinal mucosal dysfun...BACKGROUND Intestinal mucosal barrier dysfunction plays an important role in the pathogenesis of ulcerative colitis(UC).Recent studies have revealed that impaired autophagy is associated with intestinal mucosal dysfunction in the mucosa of colitis mice.Resveratrol exerts anti-inflammatory functions by regulating autophagy.AIM To investigate the effect and mechanism of resveratrol on protecting the integrity of the intestinal mucosal barrier and anti-inflammation in dextran sulfate sodium(DSS)-induced ulcerative colitis mice.METHODS Male C57BL/6 mice were divided into four groups:negative control group,DSS model group,DSS+resveratrol group,and DSS+5-aminosalicylic acid group.The severity of colitis was assessed by the disease activity index,serum inflammatory cytokines were detected by enzyme-linked immunosorbent assay.Colon tissues were stained with haematoxylin and eosin,and mucosal damage was evaluated by mean histological score.The expression of occludin and ZO-1 in colon tissue was evaluated using immunohistochemical analysis.In addition,the expression of autophagy-related genes was determined using reverse transcription-polymerase chain reaction and Western-blot,and morphology of autophagy was observed by transmission electron microscopy.RESULTS The resveratrol treatment group showed a 1.72-fold decrease in disease activity index scores and 1.42,3.81,and 1.65-fold decrease in the production of the inflammatory cytokine tumor necrosis factor-α,interleukin-6 and interleukin-1β,respectively,in DSS-induced colitis mice compared with DSS group(P<0.05).The expressions of the tight junction proteins occludin and ZO-1 in DSS model group were decreased,and were increased in resveratrol-treated colitis group.Resveratrol also increased the levels of LC3B(by 1.39-fold compared with DSS group)and Beclin-1(by 1.49-fold compared with DSS group)(P<0.05),as well as the number of autophagosomes,which implies that the resveratrol may alleviate intestinal mucosal barrier dysfunction in DSS-induced UC mice by enhancing autophagy.CONCLUSION Resveratrol treatment decreased the expression of inflammatory factors,increased the expression of tight junction proteins and alleviated UC intestinal mucosal barrier dysfunction;this effect may be achieved by enhancing autophagy in intestinal epithelial cells.展开更多
AIM： To evaluate the role of microcirculatory disorder （MCD） and the therapeutic effectiveness ;of tetramethylpyrazine （TMP） on intestinal mucosa injury in rats with acute necrotizing pancreatitis （ANP）.METHODS...AIM： To evaluate the role of microcirculatory disorder （MCD） and the therapeutic effectiveness ;of tetramethylpyrazine （TMP） on intestinal mucosa injury in rats with acute necrotizing pancreatitis （ANP）.METHODS： A total of 192 Sprague-Dawley rats were randomly divided into three groups： normal control group （C group）, ANP group not treated with TMP （P group）, ANP group treated with TMP （T group）. An ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane （4 mL/kg）. C group received isovolumetric injection of 9 g/L physiological saline solution using the same method. T group received injection of TMP （10 mL/kg） via portal vein. Radioactive biomicrosphere technique was used to measure the blood flow at 0.5, 2, 6 and 12 h after the induction of ANP. Samples of pancreas, distal ileum were collected to observe pathological changes using a validated histology score. Intestinal tissues were also used for examination of myeloperoxidase （MPO） expressed intraceUularly in azurophilic granules of neutrophils.RESULTS： The blood flow was significantly lower in P group than in C group （P 〈 0.01）. The pathological changes were aggravated significantly in P group. The longer the time, the severer the pathological changes. The intestinal MPO activities were significantly higher in P group than in C group （P 〈 0.01）. The blood flow of intestine was significantly higher in T group than in P group after 2 h （P 〈 0.01）. The pathological changes were alleviated significantly in T group. MPO activities were significantly lower in T group than in P group （P 〈 0.01 or P 〈 0.05）. There was a negative correlation between intestinal blood flow and MPO activity （r = -0.981, P 〈 0.01） as well as between intestinal blood flow and pathologic scores （r = -0.922, P 〈 0.05）.CONCLUSION： MCD is an important factor for intestinal injury in ANP. TMP can ameliorate the condition of MCD and the damage to pancreas and intestine.展开更多
AIM:To investigate dynamic changes of serum IL-2, IL-10, IL-2/IL-10 and sFas in rats with acute necrotizing pancreatitis. To explore the expression of Fas in intestinal mucosa of rats with acute necrotizing pancreatit...AIM:To investigate dynamic changes of serum IL-2, IL-10, IL-2/IL-10 and sFas in rats with acute necrotizing pancreatitis. To explore the expression of Fas in intestinal mucosa of rats with acute necrotizing pancreatitis (ANP). METHODS:A total of 64 Sprague-Dawley (SD) rats were randomly divided into two groups:normal control group (C group), ANP group (P group). An ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane. Normal control group received isovolumetric injection of 9 g/L physiological saline solution using the same method. The blood samples of the rats in each group were obtained via superior mesenteric vein to measure levels of IL-2, IL-10, sFas and calculate the value of IL-2/IL-10. The levels of IL-2, IL-10 and sFas were determined by ELISA. The severity of intestinal mucosal injury was evaluated by pathologic score. The expression of Fas in intestinal mucosal tissue was determined by immunohistochemistry staining. RESULTS:Levels of serum IL-2 were significantly higher in P group than those of C group (2.79 ± 0.51 vs 3.53 ± 0.62, 2.93 ± 0.89 vs 4.35 ± 1.11, 4.81 ± 1.23 vs 6.94 ± 1.55 and 3.41 ± 0.72 vs 4.80 ± 1.10, respectively, P < 0.01, for all) and its reached peak at 6 h. Levels of serum IL-10 were significantly higher in P group than those of C group at 6 h and 12 h (54.61 ± 15.81 vs 47.34 ± 14.62, 141.15 ± 40.21 vs 156.12 ± 43.10, 89.18 ± 32.52 vs 494.98 ± 11.23 and 77.15 ± 22.60 vs 93.28 ± 25.81, respectively, P < 0.01, for all). The values of IL-2/IL-10 were higher significantly in P group than those of C group at 0.5 h and 2 h (0.05 ± 0.01 vs 0.07 ± 0.02 and 0.02 ± 0.01 vs 0.03 ± 0.01, respectively, P < 0.01, for all), and it were significantly lower than those of C group at 6 h (0.05 ± 0.02 vs 0.01 ± 0.01, P < 0.01) and returned to the control level at 12 h (0.04 ± 0.01 vs 0.05 ± 0.02, P > 0.05). In sFas assay, there was no significant difference between P group and C group (3.16 ± 0.75 vs 3.31 ± 0.80, 4.05 ± 1.08 vs 4.32 ± 1.11, 5.93 ± 1.52 vs 5.41 ± 1.47 and 4.62 ± 1.23 vs 4.44 ± 1.16, respectively, P > 0.05, for all). Comparison of P group and C group, the pathological changes were aggravated significantly in P group. Immunohistochemistry staining show the expression of Fas was absent in normal intestinal tissues, however, it gradually increased after induction of pancreatitis in intestinal tissue, then reached their peaks at 12 h.CONCLUSION:Fas were involved in the pathogenesis of pancreatitis associated intestinal injury. The mechanisms of Fas may be associated to Fas mediated T helper cell apoptosis.展开更多
文摘Chemotherapy-induced intestinal mucositis(IM)is a prevalent complication affecting up to 80%of cancer patients undergoing treatment.Current therapies focus on symptomatic relief rather than addressing the underlying mechanism.Recent advances in integrative medicine highlight the potential of traditional Chinese medicine formulations as alternatives or adjuncts to existing therapies.In this context,this editorial discusses the recent results of a study published by Qiu et al,which investigates the multifaceted potential of modified Pulsatilla decoction(PD),a formulation of PD with licorice(Glycyrrhiza uralensis)and Ejiao(Colla corii asini),on 5-fluorouracil-induced IM in mice to alleviate clinical symptoms including diarrhea,weight loss,and intestinal damage.A series of histological,biochemical,bioinformatic,and microbiological assays evaluated body weight,diarrhea scores,inflammatory cytokine profiles,oxidative stress modulation,and microbiota composition.The findings indicated a reduction in diarrhea and oxidative stress,as well as an improvement in body weight and intestinal histopathology.Furthermore,the modified PD suppressed the TLR4/MyD88/nuclear factor kappa-B inflammatory pathway and down-regulated key proinflammatory cytokines.Moreover,the study underscores the role of gut microbiota in IM pathogenesis.Modified PD treatment reshaped microbial diversity by promoting beneficial genera such as Bacteroides acidifaciens while suppressing pathogenic species like Salmonella.These findings suggest that the therapeutic effects of the modified PD extend beyond inflammation modulation to encompass microbiome reprogramming and mucosal barrier repair.Although the study provides significant insights,several limitations still prevail.The broader implications of modified PD in gastrointestinal disorders and integrative oncology need further exploration.
基金Supported by Basic and Applied Basic Research Foundation of Guangdong Province,No.2021B1515140043,No.2022A1515140124 and No.2023A1515140115.
文摘BACKGROUND Modified Pulsatilla decoction(PD),a PD with licorice and ejiao,is a classic Traditional Chinese Medicine formula with significant efficacy in treating intestinal mucositis(IM)induced by tumor therapy.However,its specific molecular and biological mechanisms remain unclear.AIM To investigate the therapeutic effect and mechanism of modified PD in IM.METHODS This study used an IM mouse model established using 5-fluorouracil injections to investigate the effects of the modified PD(3,6,and 12 g/kg)in IM.The primary chemical components of the modified PD were identified using liquid chromatography-mass spectrometry.Body weight loss,diarrhea scores,intestinal length,histopathological scores,and inflammatory cytokine levels were measured to evaluate the effects of the modified PD in IM.Effects on the TLR4/MyD88/NF-κB pathway were evaluated using western blot analysis.The intestinal microbiota was characterized using Illumina NovaSeq sequencing.RESULTS The results showed that modified PD significantly improved weight loss and diarrhea and shortened the intestines in IM mice.Mechanistically,modified PD suppressed the TLR4/MyD88/NF-κB pathway and downregulated the expression of reactive oxygen species,lipopolysaccharides,and pro-inflammatory cytokines(IL-1β,TNF-α,IFN-γ,IL-6,IL-8,and IL-17),while increasing the expression of the anti-inflammatory cytokine IL-10.Furthermore,modified PD protected the intestinal mucosal barrier by increasing the expression of tight junction proteins(occludin-1,claudin-1,and ZO-1)and mucin-2.Finally,16S rDNA sequencing revealed that modified PD improved intestinal dysbiosis.CONCLUSION Our research offers new insights into the potential mechanism of modified PD in alleviating IM and provides experimental evidence supporting its pharmaceutical application in clinical IM treatment.
基金supported by the National Natural Science Foundation of China(No.82030118,82074232,81830120,81774095and 8170388)the Project of Shanghai Science and Technology Committee(No.19401972200)Shanghai Training Project for Leading Talents of Traditional Chinese Medicine(No.ZY[2018-2020]-RCPY-1024)。
文摘Objective:The present study investigated how mild moxibustion treatment affects the intestinal Microbiome and expression of NLRP3-related immune factors in a rat model of intestinal mucositis(IM)induced with 5-fluorouracil(5-Fu).Methods:Forty male Sprague-Dawley rats were randomly divided into control,chemotherapy,moxibustion and probiotics groups.The IM rat model was established by intraperitoneal injection of 5-Fu.Mild moxibustion treatment and intragastric probiotic administration were provided once daily for 15 days.Tissue morphology,serum levels of inflammatory factors and the expression levels of tight junction proteins,caspase-1,gasdermin D and NLRP3 were evaluated in colon tissue,through hematoxylin and eosin staining,electron microscopy,enzyme-linked immunosorbent assay,Western blotting,quantitative realtime reverse transcription polymerase chain reaction and immunofluorescence.Gut microbiome profiling was conducted through 16 S rRNA amplicon sequencing.Results:Moxibustion and probiotic treatments significantly increased the expression levels of tight junction proteins,reduced cell apoptosis and the expression levels of caspase-1,gasdermin D and NLRP3;they also decreased the serum levels of tumor necrosis factor-α,interleukin(IL)-6,IL-1βand IL-18,while increasing serum levels of IL-10.Moxibustion and probiotic treatments also corrected the reduction inα-diversity andβ-diversity in IM rats,greatly increased the proportion of the dominant bacterial genus Lactobacillus and reduced the abundance of the genera Roseburia and Escherichia in chemotherapytreated rats to levels observed in healthy animals.We also found that these dominant genera were firmly correlated with the regulation of pyroptosis-associated proteins and inflammatory factors.Finally,moxibustion and probiotic treatments elicited similar effects in regulating intestinal host-microbial homeostasis and the expression of NLRP3 inflammasome-related factors.Conclusion:Moxibustion exerts its therapeutic effect on IM by ameliorating mucosal damage and reducing inflammation.Moreover,moxibustion modulates the gut microbiota,likely via decreasing the expression levels of the NLRP3 inflammasome.
基金Supported by the National Natural Science Foundation of China,No.81673795.
文摘BACKGROUND Radiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients.However,they can also damage normal cells and cause serious intestinal toxicity,leading to gastrointestinal mucositis[1].Traditional Chinese medicine is effective in improving the side effects of chemotherapy.Wumei pills(WMP)was originally documented in the Treatise on Exogenous Febrile Diseases.It has a significant effect on chronic diarrhea and other gastrointestinal diseases,but it is not clear whether it affects chemotherapy induced intestinal mucositis(CIM).AIM To explore the potential mechanism of WMP in the treatment of CIM through experimental research.METHODS We used an intraperitoneal injection of 5-fluorouracil(5-Fu)to establish a CIM mouse model and an oral gavage of WMP decoction(11325 and 22650 mg/kg)to evaluate the efficacy of WMP in CIM.We evaluated the effect of WMP on CIM by observing the general conditions of the mice(body weight,food intake,spleen weight,diarrhea score,and hematoxylin and eosin stained tissues).The expression of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β,and myeloperoxidase(MPO),as well as the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB(TLR4/MyD88/NF-κB)signaling pathway proteins and tight junction proteins(zonula occludens-1,claudin-1,E-cadherin,and mucin-2)was determined.Furthermore,intestinal permeability,intestinal flora,and the levels of short-chain fatty acids(SCFA)were also assessed.RESULTS WMP effectively improved the body weight,spleen weight,food intake,diarrhea score,and inflammatory status of the mice with intestinal mucositis,which preliminarily confirmed the efficacy of WMP in CIM.Further experiments showed that in addition to reducing the levels of TNF-α,IL-1β,IL-6,and MPO and inhibiting the expression of the TLR4/MyD88/NF-κB pathway proteins,WMP also repaired the integrity of the mucosal barrier of mice,regulated the intestinal flora,and increased the levels of SCFA(such as butyric acid).CONCLUSION WMP can play a therapeutic role in CIM by alleviating inflammation,restoring the mucosal barrier,and regulating gut microbiota.
文摘Restoring the balance of gut microbiota has emerged as a critical strategy in treating intestinal disorders,with probiotics playing a pivotal role in maintaining bacterial equilibrium.Surgical preparations,trauma,and digestive tract reconstruction associated with intestinal surgeries often disrupt the intestinal flora,prompting interest in the potential role of probiotics in postoperative recovery.Lan et al conducted a prospective randomized study on 60 patients with acute appendicitis,revealing that postoperative administration of Bacillus licheniformis capsules facilitated early resolution of inflammation and restoration of gastrointestinal motility,offering a novel therapeutic avenue for accelerated postoperative recovery.This editorial delves into the effects of perioperative probiotic supplementation on physical and intestinal recovery following surgery.Within the framework of enhanced recovery after surgery,the exploration of new probiotic supplementation strategies to mitigate surgical complications and reshape gut microbiota is particularly intriguing.
基金Liaoning Provincial Department of Education Project-General Project(LJKMZ20221060)National Key R&D Program of China(2022YFD1600505).
文摘The intestinal mucosa is the intestinal lumen tissue that protects the intestine from invasion,maintains intestinal barrier function,and participates in the immune response.Diseases such as inflammatory enteritis and intestinal infections can cause damage to the intestinal mucosal barrier and dysfunction.The aim of this study was to investigate the improvement mechanism of malvidin-3-O-galactoside(M3G)on small intestinal mucosal barrier function.C57BL/6J male mice were given dextran sodium sulfate(DSS)for 7 days to induce enteritis,and then were fed normally with or without M3G supplementation for another 7 days.The results showed that M3G supplementation significantly improved the disease activity index(DAI)score and small intestinal tissue injury in mice with DSS induced enteritis.M3G ameliorated the small intestinal mucosal mechanical barrier function by modulating the expression of mucin 2(MUC2),zona occludens 1(ZO-1),Occludin,Claudin-1,intestinal fatty acid binding protein(iFABP),and trefoil factor 3(TFF3)in the small intestine mucosa,and the serum levels of D-lactic acid(D-LA),lipopolysaccharide(LPS),and diamine oxidase(DAO)were significantly decreased.Additionally,M3G also relieved the small intestinal immunologic barrier of mice by decreasing the immune protein levels of immunoglobulin A(IgA),immunoglobulin M(IgM),and immunoglobulin G(IgG)in serum,and secretory immunoglobulin A(SIgA)level in small intestine tissue.Furthermore,M3G inhibited the expression of Notch pathway-related proteins such as Notch1,Notch intracellular domain(NICD),delta-like ligand 4(DLL4),delta-like ligand 1(DLL1),and hairy/enhancer of split 1(Hes1).In conclusion,the results demonstrated that M3G can improve intestinal mucosal barrier function by inhibiting Notch pathway.
基金supported by the National Key Research and Development Program of China(Grant No.2022YFA1303900 to S.Y.)the National Natural Science Foundation of China(Grant Nos.32270921 and 82070567 to S.Y.and 82204354 to Y.H.)+5 种基金the Open Project of the State Key Laboratory of Reproductive Medicine of Nanjing Medical University(Grant No.SKLRM-2021B3 to S.Y.)the Talent Cultivation Project of"Organized Scientific Research"of Nanjing Medical University(Grant No.NJMURC20220014 to S.Y.)the Natural Science Foundation of Jiangsu Province(Grant No.BK20221352 to B.W.)the Jiangsu Provincial Outstanding Postdoctoral Program(Grant No.2022ZB419 to Y.H.)the Postdoctoral Research Funding Project of Gusu School(Grant No.GSBSHKY202104 to Y.H.)the China Postdoctoral Science Foundation(Grant No.2023T160329 to Y.H.).
文摘The intestinal mucosal barrier serves as a vital guardian of the gut health,maintaining a delicate equilibrium between gut microbiota and host immune homeostasis.Gasdermin D(GSDMD),a key executioner of pyroptosis downstream of the inflammasome,has been found to play intricate roles in modulating colitis by influencing intestinal macrophages and regulating mucus secretion from goblet cells.However,the exact nature of the regulatory function of GSDMD in maintaining intestinal immune homeostasis and defending against pathogens remains to be elucidated.In the current study,by using the Citrobacter rodentium infection model,we found that GSDMD played a key role in the defense against intestinal Citrobacter rodentium infection,with high expression levels in intestinal epithelial and lamina propria myeloid cells.Our results showed that GSDMD acted specifically in intestinal epithelial cells to combat the infection,independently of its effects on antimicrobial peptides or mucin secretion.Instead,the resistance was mediated by the N-terminal fragment of GSDMD,highlighting its importance in intestinal immunity.However,the specific mechanism underlying the N-terminal activity of GSDMD in protecting against intestinal bacterial infections requires future investigation.
基金National Natural Science Foundation of China:Study on the Effect of Supplementing Qi and Invigorating the Spleen on the Migration of Small Intestinal Epithelial Cells through the Regulation of Polyamines and Calcium Ions (No. 81673940)First-class Discipline Construction Major Project of Guangzhou University of Chinese Medicine,Guangzhou University of Chinese Medicine Planning (2020) No. 62:based on the Viscous Characteristics of Dampness and Pathogenic Factors in Lingnan,this Paper Studied the Differential Characteristics of the Syndrome of Deficiency of Spleen and Stomach Disease and the Intervention Mechanism of Lingnan Traditional Chinese Medicine for Mucosal Damage Repair。
文摘OBJECTIVE: To investigate the mechanism and effect of Renshen(Radix Ginseng) polysaccharide on the migration of intestinal epithelial cell line 6(IEC-6), as well as the repair mechanism of Renshen(Radix Ginseng) polysaccharide on colonic injury induced by dextran sulfate sodium(DSS) in mice. METHODS: Mice were fed 3%(w/v) DSS for 6 d to create colonic lesions. A cell-migration model was created using cell scratching. m RNA expression, protein expression, translation efficiency of m RNA, and nucleoplasmic distribution of human antigen R(Hu R) were determined by real-time reverse transcription-quantitative polymerase chain reaction, western blotting, a dual luciferase reporter system, and immunofluorescence staining, respectively. RESULTS: Renshen(Radix Ginseng) polysaccharide promoted the migration of IEC-6 cells and affected expression of stromal interaction molecule 1(STIM1) and cell division cycle 42(Cdc42) at transcriptional and posttranscriptional levels. CONCLUSIONS: Renshen(Radix Ginseng) polysaccharideinduced repair of intestinal mucosal injury may be mediated by increased cell migration via polyaminebased regulatory mechanisms. In vitro and in vivo experiments suggest that Renshen(Radix Ginseng) polysaccharide-induced post-transcriptional regulation of STIM1 and Cdc42 may be related to differences in the regulation of different target genes by Hu R. Taken together, these data provide a reference for further exploration of the protective effect of Renshen(Radix Ginseng) on the intestinal mucosa.
基金the Natural Science Foundation of Hainan Province,No.823MS046the Talent Program of Hainan Medical University,No.XRC2022007.
文摘BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology.Alkaline sphingomyelinase(alk-SMase)is specifically expressed by intestinal epithelial cells,and has been reported to play an anti-inflammatory role.However,the underlying mechanism is still unclear.AIM To explore the mechanism of alk-SMase anti-inflammatory effects on intestinal barrier function and oxidative stress in dextran sulfate sodium(DSS)-induced colitis.METHODS Mice were administered 3%DSS drinking water,and disease activity index was determined to evaluate the status of colitis.Intestinal permeability was evaluated by gavage administration of fluorescein isothiocyanate dextran,and bacterial translocation was evaluated by measuring serum lipopolysaccharide.Intestinal epithelial cell ultrastructure was observed by electron microscopy.Western blotting and quantitative real-time reverse transcription-polymerase chain reaction were used to detect the expression of intestinal barrier proteins and mRNA,respectively.Serum oxidant and antioxidant marker levels were analyzed using commercial kits to assess oxidative stress levels.RESULTS Compared to wild-type(WT)mice,inflammation and intestinal permeability in alk-SMase knockout(KO)mice were more severe beginning 4 d after DSS induction.The mRNA and protein levels of intestinal barrier proteins,including zonula occludens-1,occludin,claudin-3,claudin-5,claudin-8,mucin 2,and secretory immunoglobulin A,were significantly reduced on 4 d after DSS treatment.Ultrastructural observations revealed progressive damage to the tight junctions of intestinal epithelial cells.Furthermore,by day 4,mitochondria appeared swollen and degenerated.Additionally,compared to WT mice,serum malondialdehyde levels in KO mice were higher,and the antioxidant capacity was significantly lower.The expression of the transcription factor nuclear factor erythroid 2-related factor 2(Nrf2)in the colonic mucosal tissue of KO mice was significantly decreased after DSS treatment.mRNA levels of Nrf2-regulated downstream antioxidant enzymes were also decreased.Finally,colitis in KO mice could be effectively relieved by the injection of tertiary butylhydroquinone,which is an Nrf2 activator.CONCLUSION Alk-SMase regulates the stability of the intestinal mucosal barrier and enhances antioxidant activity through the Nrf2 signaling pathway.
基金funded by the Medical and Health Suitable Technology Development and Extension Project of Guangxi(No.S2021096)the Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer.
文摘Background:The aim of this study was to investigate the effects of different minimally invasive surgical procedures on intestinal muco-sal barrier function.Methods:In this study,76 patients who underwent minimally invasive gastric cancer surgery were selected,and peripheral blood was collected to test the levels of serum plasma D-lactic acid,diamine oxidase,and bacterial endotoxin before and 1 and 3 days after sur-gery.These markers were compared at different time points before and after surgery to understand the recovery of the intestinal muco-sal barrier function in patients after surgery.Results:On the first postoperative day,the change in serum D-lactic acid relative to the preoperative levels was significantly(P<0.05)lower in the laparoscopic surgery group(4.05[-0.195,6.917 mmol/L])than in the robot-assisted surgery group(7.56[5.190,12.145 mmol/L]).Both the serum D-lactic acid and bacterial endotoxin levels were significantly higher on the first postoperative day compared with preoperative levels,and although they showed a gradual decrease by the third day,they remained significantly higher than the pre-operative levels(P<0.05).The Student-Newman-Keuls method for pairwise comparison of the measurements at each time point dem-onstrated that the differences in D-lactic acid and bacterial endotoxin levels between the preoperative sample and the sample collected on the third postoperative day were statistically significant(P<0.05).Conclusions:Compared with the laparoscopic surgery group,the robotic surgery group showed larger changes in the postoperative serum D-lactic acid level,suggesting that the robotic surgery resulted in greater damage to the barrier function of the intestinal mucosa.The serum D-lactic acid and bacterial endotoxin levels were significantly higher in postoperative patients and showed a trend to gradually decrease,suggesting that the intestinal mucosal barrier function of patients after minimally invasive gastric cancer surgery is damaged and then gradually recovers.
基金Research Topic on traditional Chinese medicine and ethnic medicine science and technology of Guizhou Provincial Administration of Traditional Chinese Medicine(Project No.:QZYY-2024-100)。
文摘Ulcerative colitis(UC)is a chronic inflammatory bowel diseasethat significantly affects the quality of life of patients.Traditional treatments often have limitations,and alternative therapies are being explored.Miao Medicine,particularly Jinlong Zhi Xie Fang Enema,is a traditional herbal remedy used to treat UC symptoms,especially in patients with Large Intestine Damp-Heat Syndrome.However,clinical evidence supporting its efficacy is limited.
基金financial support of the Natural Science Foundation of Hunan Province(2023JJ60481)the Natural Science Foundation of Changsha Municipality(kq2208181)+3 种基金the Hunan Provincial Department of Education’s Outstanding Youth Science Research Project(22B0360)the Hunan Provincial Department of Education’s Science Research Project(22C0191)the National Ministry of Agriculture’s Edible Lily Longshan Comprehensive Experimental Station Project(CARS-21)the Hunan University of Chinese Medicine Graduate Innovation Project(2023CX157)。
文摘The incidence rate and harmfulness of depression are increasing yearly,and the research on the antidepressant effect of regulating the intestinal microecology balance has attracted widespread attention.The purpose of this research was to study the preventive effects and the regulatory mechanism of edible Lilium-egg yolk compound powder(BHT)on gut-brain crosstalk in depressive rats induced by chronic unpredictable mild stress(CUMS)through the“microbiota-gut-brain”axis.Results showed that infusion of BHT for 21 days ameliorated the morphology of the hippocampus and colon,increased the rate of sucrose preference,reduced the immobility time of forced swimming,increased the expression level of anti-inflammatory cytokine interleukin(IL)-10 in serum,up-regulated the expression level of plasma neurotransmitter 5-hydroxytryptamine(5-HT),downregulated the expression of inflammatory factors tumor necrosis factor-α(TNF-α),IL-6,and IL-1βand neurotransmitter glutamic acid(Glu)in serum,and decreased the expression levels of lipopolysaccharide(LPS),diamine oxidase(DAO)and lactate dehydrogenase(LD)in plasma.The underlying mechanism may be to reduce the activation of microglia(lower levels of CD11 antigen-like family member B(CD11b),ionized calcium binding adaptor molecule 1(Iba1)protein and gene expression),regulate hippocampal glucocorticoid receptor/brain-derived neurotrophic factor/neuropeptide Y(GR/BDNF/NPY)signaling pathway(higher levels of GR,BDNF,NPY protein and gene expression),enhance intestinal mucosal barrier function(higher levels of ZO-1,occludin protein and gene expression),regulate the composition and structure of intestinal flora(analysis results of linear discriminant analysis effect size(LEf Se)combined with random forest showed that Prevotella and Paraprevotella might be biomarkers of BHT intervention in depression),and it is related to the improvement of glutathione metabolism,and other metabolic pathways.Pearson correlation analysis found that 5-HT is strongly positively correlated with Prevotella,and Glu has a strong negative correlation with Prevotella.In conclusion,BHT can exert its antidepressant effect on CUMS-induced rats through microbiota-gut-brain interaction,can be used as an alternative to food recuperation for human depression.
基金Supported by the Zhejiang Provincial Natural Science Foundation,No.LZ22H270001.
文摘BACKGROUND Hepatic fibrosis(HF)represents a pivotal stage in the progression and potential reversal of cirrhosis,underscoring the importance of early identification and therapeutic intervention to modulate disease trajectory.AIM To explore the complex relationship between chronic hepatitis B(CHB)-related HF and gut microbiota to identify microbiota signatures significantly associated with HF progression in CHB patients using advanced machine learning algorithms.METHODS This study included patients diagnosed with CHB and classified them into HF and non-HF groups based on liver stiffness measurements.The HF group was further subdivided into four subgroups:F1,F2,F3,and F4.Data on clinical indicators were collected.Stool samples were collected for 16S rRNA sequencing to assess the gut microbiome.Microbiota diversity,relative abundance,and linear discriminant analysis effect size(LEfSe)were analyzed in different groups.Correlation analysis between clinical indicators and the relative abundance of gut microbiota was performed.The random forest and eXtreme gradient boosting algorithms were used to identify key differential gut microbiota.The Shapley additive explanations were used to evaluate microbiota importance.RESULTS Integrating the results from univariate analysis,LEfSe,and machine learning,we identified that the presence of Dorea in gut microbiota may be a key feature associated with CHB-related HF.Dorea possibly serves as a core differential feature of the gut microbiota that distinguishes HF from non-HF patients,and the presence of Dorea shows significant variations across different stages of HF(P<0.05).The relative abundance of Dorea significantly decreases with increasing HF severity(P=0.041).Moreover,the gut microbiota composition in patients with different stages of HF was found to correlate with several liver function indicators,such asγ-glutamyl transferase,alkaline phosphatase,total bilirubin,and the aspartate aminotransferase/alanine transaminase ratio(P<0.05).The associated pathways were predominantly enriched in biosynthesis,degradation/utilization/assimilation,generation of precursors,metabolites,and energy,among other categories.CONCLUSION HF affects the composition of the gut microbiota,indicating that the gut microbiota plays a crucial role in its pathophysiological processes.The abundance of Dorea varies significantly across various stages of HF,making it a potential microbial marker for identifying HF onset and progression.
文摘BACKGROUND： The gut is capable of inducing multiple organ dysfunction syndrome （MODS）. In the diagnosis and treatment of critical ill patients, doctors should pay particular attention to the protection or recovery of intestinal barrier function. However, no reliable diagnostic criteria are available clinically. This study aimed to assess the changes of intestinal mucosal barrier function in surgically critical ill patients as well as their signi？ cance.METHODS： Thirty-eight surgically critical ill patients were enrolled as a study group （APACHE II〉8 scores）, and 15 non-critical ill patients without intestinal dysfunction were selected as a control group （APACHE II〈6）. General information, symptoms, physical signs, and APACHE II scores of the patients were recorded. The patients in the study group were subdivided into an intestinal dysfunction group （n=26） and a non-intestinal dysfunction group （n=12）. Three ml venous blood was collected from the control group on admission and the same volume of plasma was collected from the study group both on admission and in the period of recovery. The plasma concentrations of endotoxin, diamine oxidase （DAO）, D-lactate, and intestinal fatty-acid binding protein （iFABP） were detected respectively. The data collected were analyzed by the SPSS 17.0 software for Windows. RESULTS： The levels of variables were significantly higher in the study group than in the control group （P〈0.01）. They were higher in the intestinal dysfunction group than in the non-intestinal dysfunction group （DAO P〈0.05, endotoxin, D-lactate, iFABP P〈0.01）. In the non-intestinal dysfunction group compared with the control group, the level of endotoxin was not significant （P〉0.05）, but the levels of DAO, D-lactate and iFABP were statistically significant （P〈0.05）. The levels of variables in acute stage were higher than those in recovery stage （P〈0.01）.The death group showed higher levels of variables than the survival group （endotoxin and D-lactate P〈0.01, DAO and iFABP P〈0.05）.CONCLUSION： The plasma concentrations of endotoxin, DAO, D-lactate, and intestinal fatty-acid binding protein （iFABP） could re？ ect a better function of the intestinal mucosa barrier in surgically critical ill patients.
基金supported by the National Natural Science Foundation of China(grant no.81774449).
文摘Intestinal microecology is the main component of human microecology.Intestinal microecology consists of intestinal microbiota,intestinal epithelial cells,and intestinal mucosal immune system.These components are interdependent and establish a complex interaction network that restricts each other.According to the impact on the human body,there are three categories of symbiotic bacteria,opportunistic pathogens,and pathogenic bacteria.The intestinal microecology participates in digestion and absorption,and material metabolism,and inhibits the growth of pathogenic microorganisms.It also acts as the body’s natural immune barrier,regulates the innate immunity of the intestine,controls the mucosal barrier function,and also participates in the intestinal epithelial cells’physiological activities such as hyperplasia or apoptosis.When the steady-state balance of the intestinal microecology is disturbed,the existing core intestinal microbiota network changes and leads to obesity,diabetes,and many other diseases,especially irritable bowel syndrome,inflammatory bowel disease(IBD),and colorectal malignancy.Intestinal diseases,including tumors,are particularly closely related to intestinal microecology.This article systematically discusses the research progress on the relationship between IBD and intestinal microecology from the pathogenesis,treatment methods of IBD,and the changes in intestinal microbiota.
基金Supported by Scientific and Technical Research Funds from Chinese PLA during the Eleventh Five-Year Plan Period,No. 2008G093National Natural Science Foundation of China,No. 30900715National Science and Technology Ministry,No. 2009BAI85B03
文摘AIM:To study whether over-starvation aggravates intestinal mucosal injury and promotes bacterial and endotoxin translocation in a high-altitude hypoxic environment.METHODS:Sprague-Dawley rats were exposed to hy-pobaric hypoxia at a simulated altitude of 7000 m for 72 h.Lanthanum nitrate was used as a tracer to detect intestinal injury.Epithelial apoptosis was observed with terminal deoxynucleotidyl transferase dUTP nick end labeling staining.Serum levels of diamino oxidase(DAO),malondialdehyde(MDA),glutamine(Gln),superoxide dismutase(SOD) and endotoxin were measured in intestinal mucosa.Bacterial translocation was detected in blood culture and intestinal homogenates.In addition,rats were given Gln intragastrically to observe its protective effect on intestinal injury.RESULTS:Apoptotic epithelial cells,exfoliated villi and inflammatory cells in intestine were increased with edema in the lamina propria accompanying effusion of red blood cells.Lanthanum particles were found in the intercellular space and intracellular compartment.Bacterial translocation to mesenteric lymph nodes(MLN) and spleen was evident.The serum endotoxin,DAO and MDA levels were significantly higher while the serum SOD,DAO and Gln levels were lower in intestine(P< 0.05).The bacterial translocation number was lower in the high altitude hypoxic group than in the high altitude starvation group(0.47±0.83 vs 2.38±1.45,P<0.05).The bacterial translocation was found in each organ,especially in MLN and spleen but not in peripheral blood.The bacterial and endotoxin translocations were both markedly improved in rats after treatment with Gln.CONCLUSION:High-altitude hypoxia and starvation cause severe intestinal mucosal injury and increase bacterial and endotoxin translocation,which can be treated with Gln.
基金Supported by National Natural Science Foundation of China,No.81701881Nanjing Medical Science and Technology Development Foundation,No.YKK17102.
文摘BACKGROUND Intestinal mucosal barrier injury and gastrointestinal dysfunction are important causes of sepsis.However,few studies have investigated the effects of enteral underfeeding on gastrointestinal function in sepsis.Moreover,no consensus on goal enteral caloric intake has been reached in sepsis.AIM To investigate the effects of different goal caloric requirements of enteral nutrition on the gastrointestinal function and outcomes in the acute phase of sepsis.METHODS Patients were randomly assigned to receive 30%(defined as group A),60%(group B),or 100%(group C)of goal caloric requirements of enteral nutrition in this prospective pilot clinical trial.The acute gastrointestinal injury(AGI)grades,incidence of feeding intolerance(FI),daily caloric intake,nutritional and inflammatory markers,and biomarkers of mucosal barrier function were collected during the first 7 d of enteral feeding.The clinical severity and outcome variables were also recorded.RESULTS A total of 54 septic patients were enrolled.The days to goal calorie of group C(2.55±0.82)were significantly longer than those of group A(3.50±1.51;P=0.046)or B(4.85±1.68;P<0.001).The FI incidence of group C(16.5%)was higher than that of group A(5.0%)or B(8.7%)(P=0.009).No difference in the incidence of FI symptoms was found between groups A and B.The serum levels of barrier function biomarkers of group B were significantly lower than those of group A(P<0.05)on the 7th day of feeding.The prealbumin and IL-6 levels of group A were lower than those of group B(P<0.05)on the 7th day of feeding.No significant differences in the clinical outcome variables or 28-d mortality were found among the three groups.CONCLUSION Early moderate enteral underfeeding(60%of goal requirements)could improve the intestinal barrier function and nutritional and inflammatory status without increasing the incidence of FI symptoms in sepsis.However,further large-scale prospective clinical trials and animal studies are required to test our findings.Moreover,the effects of different protein intake on gastrointestinal function and outcomes should also be investigated in future work.
基金Supported by the National Natural Science Foundation of China,No.81600414Medical Health Science and Technology Project of Zhejiang Provincial Health Commission,No.2018255969Zhejiang TCM Science and Technology Project,No.2016ZA123 and No.2018ZA013.
文摘BACKGROUND Intestinal mucosal barrier dysfunction plays an important role in the pathogenesis of ulcerative colitis(UC).Recent studies have revealed that impaired autophagy is associated with intestinal mucosal dysfunction in the mucosa of colitis mice.Resveratrol exerts anti-inflammatory functions by regulating autophagy.AIM To investigate the effect and mechanism of resveratrol on protecting the integrity of the intestinal mucosal barrier and anti-inflammation in dextran sulfate sodium(DSS)-induced ulcerative colitis mice.METHODS Male C57BL/6 mice were divided into four groups:negative control group,DSS model group,DSS+resveratrol group,and DSS+5-aminosalicylic acid group.The severity of colitis was assessed by the disease activity index,serum inflammatory cytokines were detected by enzyme-linked immunosorbent assay.Colon tissues were stained with haematoxylin and eosin,and mucosal damage was evaluated by mean histological score.The expression of occludin and ZO-1 in colon tissue was evaluated using immunohistochemical analysis.In addition,the expression of autophagy-related genes was determined using reverse transcription-polymerase chain reaction and Western-blot,and morphology of autophagy was observed by transmission electron microscopy.RESULTS The resveratrol treatment group showed a 1.72-fold decrease in disease activity index scores and 1.42,3.81,and 1.65-fold decrease in the production of the inflammatory cytokine tumor necrosis factor-α,interleukin-6 and interleukin-1β,respectively,in DSS-induced colitis mice compared with DSS group(P<0.05).The expressions of the tight junction proteins occludin and ZO-1 in DSS model group were decreased,and were increased in resveratrol-treated colitis group.Resveratrol also increased the levels of LC3B(by 1.39-fold compared with DSS group)and Beclin-1(by 1.49-fold compared with DSS group)(P<0.05),as well as the number of autophagosomes,which implies that the resveratrol may alleviate intestinal mucosal barrier dysfunction in DSS-induced UC mice by enhancing autophagy.CONCLUSION Resveratrol treatment decreased the expression of inflammatory factors,increased the expression of tight junction proteins and alleviated UC intestinal mucosal barrier dysfunction;this effect may be achieved by enhancing autophagy in intestinal epithelial cells.
基金Supported by Zhenjiang Science and Technology Committee, No. SH2002015
文摘AIM： To evaluate the role of microcirculatory disorder （MCD） and the therapeutic effectiveness ;of tetramethylpyrazine （TMP） on intestinal mucosa injury in rats with acute necrotizing pancreatitis （ANP）.METHODS： A total of 192 Sprague-Dawley rats were randomly divided into three groups： normal control group （C group）, ANP group not treated with TMP （P group）, ANP group treated with TMP （T group）. An ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane （4 mL/kg）. C group received isovolumetric injection of 9 g/L physiological saline solution using the same method. T group received injection of TMP （10 mL/kg） via portal vein. Radioactive biomicrosphere technique was used to measure the blood flow at 0.5, 2, 6 and 12 h after the induction of ANP. Samples of pancreas, distal ileum were collected to observe pathological changes using a validated histology score. Intestinal tissues were also used for examination of myeloperoxidase （MPO） expressed intraceUularly in azurophilic granules of neutrophils.RESULTS： The blood flow was significantly lower in P group than in C group （P 〈 0.01）. The pathological changes were aggravated significantly in P group. The longer the time, the severer the pathological changes. The intestinal MPO activities were significantly higher in P group than in C group （P 〈 0.01）. The blood flow of intestine was significantly higher in T group than in P group after 2 h （P 〈 0.01）. The pathological changes were alleviated significantly in T group. MPO activities were significantly lower in T group than in P group （P 〈 0.01 or P 〈 0.05）. There was a negative correlation between intestinal blood flow and MPO activity （r = -0.981, P 〈 0.01） as well as between intestinal blood flow and pathologic scores （r = -0.922, P 〈 0.05）.CONCLUSION： MCD is an important factor for intestinal injury in ANP. TMP can ameliorate the condition of MCD and the damage to pancreas and intestine.
基金Zhenjiang Science and Technology Committee, No. SH2005044
文摘AIM:To investigate dynamic changes of serum IL-2, IL-10, IL-2/IL-10 and sFas in rats with acute necrotizing pancreatitis. To explore the expression of Fas in intestinal mucosa of rats with acute necrotizing pancreatitis (ANP). METHODS:A total of 64 Sprague-Dawley (SD) rats were randomly divided into two groups:normal control group (C group), ANP group (P group). An ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane. Normal control group received isovolumetric injection of 9 g/L physiological saline solution using the same method. The blood samples of the rats in each group were obtained via superior mesenteric vein to measure levels of IL-2, IL-10, sFas and calculate the value of IL-2/IL-10. The levels of IL-2, IL-10 and sFas were determined by ELISA. The severity of intestinal mucosal injury was evaluated by pathologic score. The expression of Fas in intestinal mucosal tissue was determined by immunohistochemistry staining. RESULTS:Levels of serum IL-2 were significantly higher in P group than those of C group (2.79 ± 0.51 vs 3.53 ± 0.62, 2.93 ± 0.89 vs 4.35 ± 1.11, 4.81 ± 1.23 vs 6.94 ± 1.55 and 3.41 ± 0.72 vs 4.80 ± 1.10, respectively, P < 0.01, for all) and its reached peak at 6 h. Levels of serum IL-10 were significantly higher in P group than those of C group at 6 h and 12 h (54.61 ± 15.81 vs 47.34 ± 14.62, 141.15 ± 40.21 vs 156.12 ± 43.10, 89.18 ± 32.52 vs 494.98 ± 11.23 and 77.15 ± 22.60 vs 93.28 ± 25.81, respectively, P < 0.01, for all). The values of IL-2/IL-10 were higher significantly in P group than those of C group at 0.5 h and 2 h (0.05 ± 0.01 vs 0.07 ± 0.02 and 0.02 ± 0.01 vs 0.03 ± 0.01, respectively, P < 0.01, for all), and it were significantly lower than those of C group at 6 h (0.05 ± 0.02 vs 0.01 ± 0.01, P < 0.01) and returned to the control level at 12 h (0.04 ± 0.01 vs 0.05 ± 0.02, P > 0.05). In sFas assay, there was no significant difference between P group and C group (3.16 ± 0.75 vs 3.31 ± 0.80, 4.05 ± 1.08 vs 4.32 ± 1.11, 5.93 ± 1.52 vs 5.41 ± 1.47 and 4.62 ± 1.23 vs 4.44 ± 1.16, respectively, P > 0.05, for all). Comparison of P group and C group, the pathological changes were aggravated significantly in P group. Immunohistochemistry staining show the expression of Fas was absent in normal intestinal tissues, however, it gradually increased after induction of pancreatitis in intestinal tissue, then reached their peaks at 12 h.CONCLUSION:Fas were involved in the pathogenesis of pancreatitis associated intestinal injury. The mechanisms of Fas may be associated to Fas mediated T helper cell apoptosis.
