Objective To observe the effects of San-Huang-Chai-Zhu formula on the expression of Nrf2 and oxidative stress in liver of rats with acute intrahepatic cholestasis induced by isothionaphthol(ANIT).Methods 48 male SD rats were randomly divided into the normal group,the model group,the compound high,medium,low dose group and the ursodeoxycholic acid(UDCA)group,with 8 rats in each group.On the third day of the experiment,a one-time administration of 4%ANIT 100 mg/kg was used to create the model,and different drugs were administered to each drug intervention group on the 1st to 5th day.Materials were collected 48 hours after molding.The serum liver function was detected by abdominal venous blood sampling after fasting anesthesia.The liver was isolated and stored in the refrigerator at-80℃for use.The superoxide dismutase(SOD)activity,malondialdehyde(MDA)content,glutathione peroxidase(GSH-PX)and catalase(CAT)activity were measured in liver tissue.mRNA expressions of Nrf2,SOD1,SOD2,SOD3 and CAT in liver tissue were determined by fluorescent quantitative PCR.Results Compared with the normal group,the MDA content in the liver of the model group was significantly increased,the activities of SOD,GSH-Px and CAT were significantly decreased,and the expressions of Nrf2mRNA,protein,SOD and CATmRNA in the liver were significantly decreased in the model group 48 hours after modeling(P<0.05).Compared with the model group,the content of MDA in liver of San-Huang-Chai-Zhu formula in each dose group and UDCA group was significantly decreased,the activities of SOD,GSH-Px and CAT were fully or partially increased,and the expressions of Nrf2mRNA and protein,SOD and CATmRNA were significantly increased(P<0.05).Conclusion The therapeutic mechanism of San-Huang-Chai-Zhu formula on acute intrahepatic cholestasis induced hepatic injury may be through increasing the expression of Nrf2 protein and mRNA,enhancing the antioxidant stress ability of liver,alleviating liver tissue inflammation and injury,and thus promoting the recovery of liver function.
Intrahepatic cholestasisNrf2Oxidative stressSan-Huang-Chai-Zhu formula