非酒精性脂肪肝病大鼠肠道菌群对肠促胰素效应的影响  

Influence of gut microbiota in non-alcoholic fatty liver disease rat on incretin effect

作　　者：王亚涛 程妍[1] 徐静远 史海涛[1] 王凯 鲁晓岚[1,2] WANG Ya-tao;CHENG Yan;XU Jing-yuan;SHI Hai-tao;WANG Kai;LU Xiao-lan(Department of Gastroenterology,the Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710004,Shaanxi Province,China;Department of Gastroenterology,Fudan University Pudong Medical Center,Shanghai 201399,China)

机构地区：[1]西安交通大学第二附属医院消化科,西安710004 [2]复旦大学附属浦东医院消化科,上海201399

出　　处：《复旦学报（医学版）》2022年第3期332-338,共7页Fudan University Journal of Medical Sciences

基　　金：上海市自然科学基金(20ZR1450100);上海市浦东医院人才项目(YJRCJJ201801)。

摘　　要：目的探讨非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)大鼠肠道菌群对L细胞、胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)及其受体(GLP-1R)的影响。方法将20只SD大鼠分为2组,每组10只,一组给予正常饮食(normal diet,ND),一组给予高脂饮食(high-fat diet,HFD);另将20只SD大鼠给予口服混合肠道非吸收性抗生素2周,建立伪肠道无菌大鼠模型,分为2组,每组10只,一组接受HFD组大鼠肠菌移植,另一组接受ND组大鼠肠菌移植;移植后继续高脂饮食饲养8周,第8周末称体质量并测定血脂、血糖、胰岛素水平,计算胰岛素抵抗指数,评价肝脏组织学,计数L细胞数量,检测餐后1 h门脉血和结肠组织GLP-1、肝脏和胰腺组织GLP-1R的含量,检测粪便双歧杆菌、乳杆菌、大肠埃希菌和肠球菌的数量。结果和移植ND组肠菌的大鼠相比,移植HFD组肠菌的大鼠表现出更加明显的肝脏脂肪沉积和胰岛素抵抗(P<0.05),体质量升高(P<0.01),血脂升高(P<0.05),结肠L细胞数量降低(P<0.05),GLP-1合成分泌降低(P<0.001),肝脏和胰腺GLP-1R含量降低(P<0.001),粪便双歧杆菌、乳杆菌数量减少(P<0.05),而大肠埃希菌、肠球菌数量增加(P<0.05)。结论在高脂饮食的作用下,NAFLD大鼠肠道菌群可减少结肠L细胞数量,降低大鼠GLP-1分泌和受体数量,进而促进NAFLD的发生发展。Objective To explore the influence of gut microbiota in non-alcoholic fatty liver(NAFLD)rat on L cells,glucagon-like peptide-1(GLP-1)and its receptors(GLP-1R).Methods A total of 20 SD rats were randomly divided into 2 groups(n=10 for each group),one group was fed with normal diet(ND),the other was fed with high-fat diet(HFD).Another 20 SD rats orally administered nonabsorbed antibiotics for 2 weeks to establish a pseudo germ-free rat model,and then were divided into 2 groups(n=10),one group was colonised with the gut microbiota from HFD group,the other were colonised from ND group,and both of them were then fed with high-fat diet for an additional 8 weeks after colonisation.At the end of 8th week,the body weight was measured,the serum level of blood lipids,fasting blood glucose and insulin were assayed,the insulin resistance index(HOMA-IR)was calculated,the liver histology was evaluated,the number of colonic L cells were counted,the levels of GLP-1 in 1-hour postprandial of portal blood and colonic homogenates were determined,and the levels of GLP-1R in hepatic and pancreatic homogenates were also determined.Moreover,the amount of Bifidobacterium,Lactobacillus,Escherichia coli and Enterococcus in the faecal microbiota were detected.Results Compared with rats colonised with gut microbiota from ND group,rats colonised from HFD group showed more serious hepatic fat deposition and insulin resistance(P<0.05).They had increased body weight(P<0.01)and increased blood lipids(P<0.05).They had decreased number of colonic L cells(P<0.05),decreased synthesis and secretion level of GLP-1(P<0.001),and decreased expression of GLP-1R in liver and pancrease(P<0.001).They had a decrease in Bifidobacterium and Lactobacillus(P<0.05),and an increase in Escherichia coli and Enterococcus in the feces(P<0.05).Conclusion Under HFD the gut microbiota of NAFLD can reduce the number of colonic L cells in rats.

关 键 词：非酒精性脂肪肝病(NAFLD) 肠道菌群 肠促胰素效应 胰高血糖素样肽-1(GLP-1) 

分 类 号：R575.5[医药卫生—消化系统]