Tanshinone D A improves acute liver injury in mice by inhibiting Grp78/caspase-12 pathway / 中国药理学通报

ABSTRACT

Aim To investigate the protective effect of tanshinone II A on endoplasmic reticulum stress-induced acute liver injury in mice based on Grp78/ caspase-12 pathway. Methods Sixty male Kunming mice were randomly divided into normal group, model group, positive drug group and tanshinone II A low, medium and high dose groups (10, 20, 40 mg • kg"1 • d"1). Tunicamycin (1 mg • kg"1) was administered to replicate the acute liver injury model in mice. The liver pathological changes and hepatocyte apoptosis were observed 24 hours after the model was established. The serum levels of inflammatory factors and the expressions of Grp78, caspase-12, caspase-3, Bcl- 2 and Bax in liver tissues were detected. Results Compared with control group, serum AST, ALT, MDA levels increased and SOD level decreased in model group. The pathological damage and hepatocyte apoptosis were observed. The expressions of Grp78, caspase-12, caspase-3 and Bax in liver increased, the expression of Bcl-2 decreased, and the mRNA levels of Grp78 and caspase-12 were elevated. After bifendate and tanshinone II A treatment, the changes of the a- bove indicators in acute liver injury mice group were reversed. Conclusions Tanshinone IIA can improve the acute liver injury induced by tunicamycin in mice by inhibiting the activation of GRP78/caspase-12 pathway in liver tissues and reducing endoplasmic reticulum stress level.