酪酸梭菌对NAFLD小鼠肠黏膜通透性的影响及相关机制  

Effect of Clostridium butyricum on Intestinal Mucosal Permeability in NAFLD Mice and Its Related Mechanism

作　　者：汪洋 李莉 WANG Yang;LI Li(First School of Clinical Medicine,Xuzhou Medical University,Xuzhou 221004,China;Affiliated Hospital of Xuzhou Medical University,Xuzhou 221006,China)

机构地区：[1]徐州医科大学第一临床医学院,江苏徐州221004 [2]徐州医科大学附属医院,江苏徐州221006

出　　处：《北华大学学报（自然科学版）》2024年第6期780-785,共6页Journal of Beihua University（Natural Science）

基　　金：江苏省社会发展重点项目(BE2020654)。

摘　　要：目的探讨酪酸梭菌(CB)对非酒精性脂肪性肝病(NAFLD)小鼠肠黏膜通透性的影响及相关机制。方法使用高脂饮食构建NAFLD小鼠模型,将小鼠分为模型组(Mod)、酪酸梭菌低剂量组(CBL,0.5×10^(7) CFU/mL)、酪酸梭菌高剂量组(CBH,1.0×10^(7) CFU/mL),同时设置正常对照组(Con),每组8只,每周记录1次小鼠体质量。末次给药完成后小鼠禁食12 h,心脏取血,取肝脏组织、小肠组织,应用酶联免疫吸附法检测小鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆固醇(TC)、甘油三酯(TG)、二胺氧化酶(DAO)水平和肝脏组织IL-6、TNF-α水平;苏木精-伊红染色观察肝脏组织病理变化;Western blot检测小肠组织中紧密连接蛋白(Occludin)、闭锁小带蛋白-1(ZO-1)蛋白表达。结果随着培养时间的延长,各组小鼠体质量均呈增长趋势,培养第4周开始,Mod小鼠体质量明显高于Con小鼠,CBL、CBH小鼠体质量较Mod小鼠均有降低(均P<0.05),CBH小鼠体质量下降幅度更为明显。Mod小鼠血清ALT、AST、TC、TG水平明显高于Con小鼠(P<0.01);CBL、CBH小鼠血清ALT、AST、TC、TG水平明显低于Mod小鼠(P<0.05),CBH小鼠下降幅度更明显。苏木精-伊红染色显示,CBL、CBH小鼠肝组织中纤维结构和肝小叶结构较Mod小鼠明显改善,脂肪沉积、细胞变性和坏死、炎症细胞浸润也明显减轻。Mod小鼠血清DAO水平及肝组织中IL-6、TNF-α水平明显高于Con小鼠(P<0.01);CBL、CBH小鼠血清DAO水平及肝组织中IL-6、TNF-α水平明显低于Mod小鼠,CBH小鼠明显低于CBL小鼠(均P<0.05)。Mod小鼠小肠组织中Occludin表达水平、ZO-1蛋白表达水平明显低于Con组小鼠(P<0.01);CBL、CBH小鼠小肠组织中Occludin、ZO-1蛋白表达水平明显高于Mod小鼠,CBH小鼠明显高于CBL小鼠(均P<0.05)。结论NAFLD小鼠肠黏膜屏障受损可导致纤维结构和肝小叶结构破坏,紧密连接表达减少,CB可通过上调Occludin、ZO-1蛋白表达增强紧密连接,进而改善肠黏�Objective To investigate the effect and related mechanism of Clostridium butyricum(CB)on intestinal mucosal permeability in non-alcoholic fatty liver disease(NAFLD)mice.Method A high-fat diet was used to construct a NAFLD mouse model,which was divided into model group and low-dose CB group(0.5×10^(7)CFU/mL),high-dose CB group(1×10^(7) CFU/mL),while setting up a normal control group with 8 mice in each group,and recording the weight of mice once a week.After the last administration,mice fasted for 12 hours,and liver and small intestine tissues were taken from the heart after blood collection.Enzyme linked immunosorbent assay was used to detect serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),triglycerides(TG),diamine oxidase(DAO)concentrations,as well as liver IL-6 and TNF-αlevel;HE staining was used to observe pathological changes in liver tissue;Western blot was used to detect the expression of tight junction protein(Occludin)and closed zone protein-1(ZO-1)in the small intestine tissue.Results With the extension of cultivation time,the weight of mice in each group showed an increasing trend.Starting from the 4th week of cultivation,the weight of Mod mice was significantly higher than that of Con mice.The weight of CBL and CBH mice decreased compared to Mod mice,and the weight loss of CBH mice was more significant(P<0.05).The serum ALT,AST,TC and TG in Mod mice were significantly higher than those in Con mice(P<0.01);CBL and CBH mice were significantly lower than Mod mice,and the decrease in CBH mice was more significant(P<0.05).HE staining showed that the fibrous structure and hepatic lobular structure in the liver tissue of CBL and CBH mice were significantly improved comparing to Mod mice,and fat deposition,cell degeneration and necrosis,and inflammatory cell infiltration were also significantly reduced.The level of serum DAO and levels of IL-6 and TNF-αin liver tissue of Mod mice were significantly higher than those of Con mice(P<0.01);The levels of serum DAO and I

关 键 词：非酒精性脂肪性肝病 酪酸梭菌 肠黏膜通透性 机制 

分 类 号：R574[医药卫生—消化系统]