Influence on Inflammation of Huoxue Qingjieling on Nonalcoholic Steatohepatitis Rats Based on TGR5/NLRP3 Signaling Pathway
OBJECTIVE Based on the G protein-coupled bile acid receptor(TGR5)/nucleotide binding oligomerization domain-like receptor 3(NLRP3)signaling pathway,to explore the mechanism of Huoxue Qingjieling in improving the inflammatory response of rats with nonalcoholic steatohepatitis(NASH).METHODS A total of 70 male SD rats were randomly divided into 5 groups,20 rats in the control group,20 rats in the model group,10 rats in each of the atorvastatin positive drug group,the high-dose and low-dose groups of Huoxue Qingjieling.The control group was given normal feed,and the rest of the groups were given high-fat diet.Through model evaluation,it was determined that the NASH rat model was successfully established at the end of the 20th week.After successful modeling,the control group and the model group were given with normal saline by intragastric administration,the atorvastatin positive drug group,and the high and low dose groups of Huoxue Qingjieling were given corresponding drugs once a day for 4 weeks.At the end of the 24th week,the rats were killed,and the changes of body weight,wet liver weight and liver index was calculated.The serum was taken to test the triglyceride(TG),total cholesterol(TC),alanine aminotransferase(ALT),and aspartic acid aminotransferase(AST)levels by automatic biochemical analyzer.Pathological changes of liver tissues were observed by HE staining and oil red O staining.The expression levels of TGR5 and NLRP3 proteins were detected by Western blotting and immunofluorescence staining.ELISA detected the content of interleukin-18(IL-18)and interleukin-1β(IL-1β)in liver tissue.RESULTS Huoxue Qingjieling could significantly improve the general state of NASH rats.Every dose group could significantly reduce the body weight,liver wet weight and liver index of rats(P＜0.01),and TG,TC content and ALT,AST activity levels of serum significantly decreased(P＜0.01).The pathological results showed that Huoxue Qingjieling could significantly improve liver steatosis,inflammation and balloon-like.The expression of TGR5 protein was significantly increased(P＜0.01),the expression of NLRP3 protein and the content of IL-18,IL-1β were significantly decreased(P＜0.01,P＜0.05).CONCLUSION Huoxue Qingjieling can significantly improve the state of NASH rats,inhibit liver steatosis and inflammation,and its mechanism may be closely related to the inhibition of TGR5/NLRP3 signaling pathway.
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