Experimental study on Jiedu Huayu Granules regulating ROS-NLRP3 signaling pathway to alleviate liver inflammatory stress in rats with liver failure
Objective To analyze the molecular mechanism of Jiedu Huayu Granules(JDHY)in improving liver inflammation in rats with liver failure by regulating ROS-NLRP3 signaling pathway.Methods Thirty-six male Wistar rats were randomly divid-ed into control group,model group and JDHY group,with 12 rats in each group.A rat model of acute liver failure was established by intraperitoneal injection of D-galactosamine(D-GalN)combined with lipopolysaccharide(LPS).JDHY group was given JDHY(57.55 g·kg-1·d-1)before modeling,continuous intragastric administration for 72 h and continued to 24 h after model-ing.Rats in each group were sacrificed 24 h after modeling.Serum and tissue samples were collected.Serum ALT,AST and TBIL levels were measured by automatic biochemical analyzer.Serum IL-1β and IL-18 were measured by ELISA.ROS pro-duction was evaluated.The expression of NLRP3 and GSDMD in liver tissue was analyzed by immunohistochemistry.The expres-sion of NLRP3,GSDMD,GSDMD-N,ASC and Caspase-1 in liver tissue was analyzed by Western blotting.Results JDHY could effectively improve liver function(ALT,AST,TBIL)(P＜0.05),reduce the excessive production of ROS(P＜0.05)and the release of inflammatory factors(IL-1β,IL-18)in rats with liver failure.In addition,compared with the model group,JDHY reduced the expression of NLRP3,GSDMD,GSDMD-N,ASC and Caspase-1 in liver tissue of rats with liver failure(P＜0.05).Conclusion JDHY can inhibit the excessive activation of ROS-NLRP3 signaling pathway,reduce the release of pro-inflammatory factors,alleviate the level of liver inflammatory stress and antagonize liver failure.
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