Study On The Effect Of Yiqi Bushen Tiaozhi Formula On Non-Alcoholic Steatohepatitis Based On IRE-1α/JNK Signal Pathway

Objective:To observe the anti-NASH effect of Yiqi Bushen Tiaozhi Formula in rats,and to investigate the effects of endoplasmic reticulum stress and IRE-1α/JNK is the starting point to explore the possible mechanism of Yiqi Bushen Tiaozhi Formula in interfering with NASH.Methods:Twenty-four SD rats were randomly divided into normal group,model group,Yishanfu group and Yiqi Bushen Tiaozhi Formula group,with 6 rats in each group.The normal group was fed with standard diet,and the other groups were fed with high-fat diet(adding 10%lard,2%cholesterol,1%bile salt,5%egg yolk powder on the basis of 82%standard diet)for 12 weeks.At the same time,the Yiqi Bushen Tiaozhi Formula group was fed with 22.12 g/Kg.d Yiqi Bushen Tiaozhi Formula fluid extract Yishanfu group was administrated with 195.4 mg/Kg.d of polyene phosphatidylcholine suspension,normal group and model group were administrated with the same volume of normal saline.The rats in each group were treated at the end of 12 weeks.Real-time-PCR technology was used to detect GRP78,IRE-1α,JNK,TNF-α and MCP-1 mRNA expression in liver tissues,Western blot technology to detect GRP78,IRE-1α,JNK and Phosphorylation level of JNK protein expression.Results:1.After high-fat diet modeling,a large number of steatosis appeared in the liver tissue of NASH model group,inflammatory cell infiltration and liver necrosis occurred in different degrees in the liver lobule tissue,at the same time,the ballooning of liver cells,NAFLD activity score(NAS)was significantly higher than the normal group(P<0.05,P<0.01),and serum AST,ALT,TC levels and liver tissue TG,TC content were significantly higher than the normal group(P<0.05,P<0.01);The inflammatory cell infiltration,hepatic necrosis and NAS in Yiqi Bushen Tiaozhi Formula and Yishanfu groups were significantly lower than those in the model group(P<0.05,P<0.01).The contents of TG and TC in liver tissue and the levels of ALT,AST and TC in serum were significantly lower than those in the model group(P<0.05,P<0.01).2.The mRNA and protein expression levels of Bip,IRE1a,JNK,TNF-a,and Mcp-1 in the liver tissue of the model group rats were significantly increased compared to the normal group(P<0.05,P<0.01).The mRNA and protein expression levels of Bip,IRE1a,JNK,and Mcp-1 genes in the Yiqi Bushen Tiaozhi Formula and Yishanfu group were significantly reduced compared to the model group(P<0.05,P<0.01).Conclusion:Yiqi Bushen Tiaozhi Formula can regulate IRE-1α/JNK signal pathway and improve endoplasmic reticulum stress and alleviate the degree of liver inflammation induced by high fat in NASH rats.