基于肠-肝轴探讨芪茵颗粒防治非酒精性脂肪肝的作用机制OA

Objective To investigate the ameliorative effect of Qiyin Granule(芪茵颗粒,QYG)on liver and intestinal pathologic injury in rats modeled for non-alcoholic fatty liver disease(NAFLD)and related mechanisms,and to clarify the dose effect.Methods The rats were divided into the control group(Group C),the model group(Group HF),the low(Group L),medium(Group M)and high(Group H)dose groups of QYG and the positive drug group(Group MT).After the rats in each group were fed with high-fat and high-sugar feed for 9 weeks to establish the NAFLD model,all groups except the blank group and the model group were given the corresponding drug interventions for 4 weeks,and the liver and intestinal tissue morphology of each group were observed by HE staining,the intestinal inflammatory factors(TNF-α,NF-κB)were detected by immunohistochemistry,the intestinal barrier markers(LPS,DAO,D-LA)were detected by enzyme kits,and the tight junction proteins(ZO-1,D-LA),ZO-1,and ZO-2 were detected by WB.junction proteins(ZO-1,Occludin),and combined with 16srDNA to analyze the diversity,composition and functional pathways of intestinal flora.Results Compared with group C,the HF group showed structural disruption of liver lobules,accumulation of lipid droplets in hepato-cytes,intestinal mucosal damage,villi atrophy,accompanied by elevated expression of TNF-α/NF-κB(P<0.01),elevated intestinal barrier markers,and down-regulation of tight junction proteins,as well as disturbed diversity of intestinal flora(Shannon elevated,Chao1 plummeted),core phylum(Firmicutes lowered,Proteobacteria elevated)The diversity of the intestinal flora was disturbed(Shannon increased,Chao1 decreased abruptly),the core phylum(Firmicutes decreased,Proteobacteria increased)and the genus level(short-chain fatty acid-producing bacteria decreased)were abnormal,and the metabolic pathway of the flora was damaged.Com-pared with HF group,M group showed the most significant improvement in the above indexes:the morphology of liver and intestinal tis-sues was close to normal,the levels of inflammatory factors and intestinal barrier markers were regulated,the expression of ZO-1/Occlu-din was up-regulated(P<0.05),and the diversity and composition of flora and its functional pathways were close to normal,which was better than that of L group and H group.Conclusion QYG can improve NAFLD by repairing the intestinal barrier,inhibiting intestinal inflammation,and regulating the structure and function of intestinal flora,with the best effect in the middle dose,which can provide an experimental basis for the clinical intervention of NAFLD.