Research Of The Effect And Mechanism Of Gegen Qinlian Decoction On Non-alcoholic Steatohepatitis Via Intestinal Liver Axis

Objective To study the effect and possible mechanisms of Gegen Qinlian Decoction on non-alcoholic steatohepatitis via gut-liver axis.Methods1.59 male C57BL/6 mice,6 weeks old,after two-week acclimation,were randomly divided into four groups,normal control group,model group,Gegen Qinlian Decoction low dose group,Gegen Qinlian Decoction high dose group.The animals were housed in an environmentally controlled room(22 to 28?).The normal control group was fed with ordinary fodderthe model group was given high-fat diet combined with DSS.In the Gegen Qinlian Decoction group,8g/kg/d,16g/kg/d of Gegen Qinlian Decoction were given for intervention at the same time of modeling.The body weight of the mice was measured every week.The whole feeding process last for 12 weeks.2.The mice were observed daily and weighed once a week.After the experiment,the levels of serum total cholesterol(TC),triglyceride(TG)and endotoxin(LPS)were measured.The liver histopathological changes were observed by HE staining,and the protein expressions associated with gut barrier were detected by Western blotting method and the changes of intestinal flora abundance and diversity were analyzed by using 16 S microbial community diversity as well.Results1.Compared with the normal control group,the body weight and liver index of the model group were significantly increased(P<0.05),and the liver weight showed increasing trend(P > 0.05).Compared with the model group,the body weight and liver index in the high and low dose of Gegen Qinlian Decoction groups were significantly reduced(P < 0.05),and the liver weight showed decreasing trend(P > 0.05).2.HE staining results: Lipid deposition and inflammative cell infiltration were obvious in the model group;The hepatic steatosis was significantly reduced in the high and low dose of Gegen Qinlian Decoction groups.3.Serum test: compared with the normal group,serum TG,TC,LDL-C and LPS levels in the model group were significantly increased(P < 0.05).Compared with the model group,serum levels of TG,LDL-C and TG were significantly decreased in the high and low dose group of Gegenqinlian Decoction(P < 0.05),while serum levels of TC and LPS were significantly decreased in the low dose group of Gegenqinlian Decoction(P <0.05).4.Western blot results: Compared with the normal control group,protein expressions of Zo-1,Occludin,Claudin-1 and CX3CR1 in intestinal tissues of the model group were significantly decreased(P < 0.05).Protein expressions of Zo-1,Occludin,Claudin-1and CX3CR1 in intestinal tissues of the high-and-low-dose of Gegen Qinlian Decoction group were significantly higher than those of the model group(P < 0.05).5.Gut microbiota: the NASH model group showed lower Chao index,Shannon index,Observed_otus index,higher ACE index and Simpson index than the normal group.Compared with the model group,the high-dose group of Gegen Qinlian Decoction showed a certain increasing trend in Chao index,Shannon index and ACE index,and a decreasing trend in Simpson index(P>0.05),while the low-dose group of Gegen Qinlian Decoction showed no change compared with the model group.Concerned with classification level,in the model group,the percents of Firmicutes,Proteobacteria,Actinobacteria,Desulfovibrio,Bactoscilla,Butyricicoccus,Des-ulfovibrionaceae,Rumin-o coccaceae were increased,the percents of bacteroidetes and bacteroides are declined;compared with the model group,Gegen Qinlian Decoction in both high and low dose groups showed some improvement.Conclusions Gegen Qinlian Decoction has a protective effect on NASH,,and its mechanism may be related with lipid metabolism,meanwhile,it shows effect on increasing gut barrier function,gut miroenvironment,and decreasing gut permeability by gut-liver axis.In this way,it could decrease the low inflammantory status in systematic circulation and improve inflammatory infiltration in NASH.