Protective effect of Rosuvastatin aginst Doxorubicin-induced mice hepatotoxicityvia Sirt1/NF-κB signal pathway

Objective To investigate the role of Sirt1/NF-κB signal pathway in doxorubicin(DOX)-induced mice hepatotoxity damage and the effect of Rosuvastatin(Ros) on this pathway. Methods Thirty male,8 weeks old,C57BL/6J mice were randomly divided into 3 groups(n=10).In DOX-treated group,the mice received intra-peritoneal injection of DOX(15 mg/kg)to build hepatotoxicity damage model,and then received intragastric normal saline for the same volume.DOX/Ros group,the mice were pre-intragastric Ros 10 mg/(kg·d)for 5 d,followed by a single intra-peritioneal injection DOX(15 mg/kg),and then post-intervention for another 5 d.Serum lipid and liver function were detected with semi-automatic biochemical instrument.The expression of SOD,MDA,Sirt1 and NF-κB were evaluated with immunohistochemical method.The morphological changes of the liver cells were observed with HE staining. Results When compared with the control group,the levels of TC,TG,LDL-C,ALT,AST and MDA in the model group were significantly increased,but LDL-C and SOD were decreased(P<0.05),and hepatocytes swelled,blood vessels congested with lymphocytic infiltration.The expression of Sirt1 in the model group significantly decreased,NF-κB significantly increased(P<0.05).Compared with the model group,the levels of TC,TG,LDL-C,ALT,AST and MDA in the intervention group significantly decreased whereas HDL-C and SOD increased(P<0.05),andhepatocytes arranged orderly.The expression of Sirt1 markedly increased,NF-κB decreased(P<0.05). Conclusion Rosuvastatin has protective effect against DOX-induced hepatotoxicity by up-regulating Sirt1 and inhibiting NF-κB.