甘草酸二铵改善Con A致小鼠肝损伤的作用研究

Protective Effect of Diammonium Glycyrrhizin on Con A-induced Liver Injury in Mice

探讨甘草酸二铵(Diammonium glycyrrhi zinate,DG)对刀豆蛋白(Concanavalin A,Con A)致小鼠肝损伤的保护作用及机制。连续给予ICR小鼠各保肝药的临床等效量7天后,再以Con A造成小鼠肝损伤。生化法检测血清中谷草转氨酶(AST)、谷丙转氨酶(ALT)含量;HE染色观察肝组织病理学特征;通过药物代谢物与转氨酶异常大鼠血清共孵育,检测DG对转氨酶活性的直接作用;免疫组化、Western blot检测肝组织中凋亡蛋白和炎性细胞因子的水平,探讨DG的保肝机制。结果显示,58. 5 mg/kg DG能够改善Con A所致小鼠肝脏病理损伤,降低小鼠血清中AST、ALT水平,而对AST、ALT的活性没有直接抑制作用;并且DG可以抑制肝细胞凋亡(下调cleaved Caspase-3、cleaved PARP以及BAX/BCL-2的表达)和炎性反应(降低TGF-β1、COX-2、IL-6、TNF-α和IFN-γ等炎性因子水平)。综上所述,DG可改善Con A致小鼠急性肝损伤,其作用机制可能与抑制细胞凋亡和炎症反应有关。

This study was to investigate the effect and the underlying mechanism of DG on the hepatotoxicity induced by Con A.In this study,a concanavalin A(Con A)-induced hepatitis mouse model was used to examine the effect of DG on hepatic injury.DG(58.5mg/kg),silymarin(36.4mg/kg)and bicyclol(9.75mg/kg)equivalent to clinical dosage were orally administered to mice once daily for7consecutive days before Con A challenge.After that,blood samples were collected for serological detection,and histological analysis was carried out by hematoxylin-eosin staining.In order to investigate the molecular mechanism of DG’s protective effect,the serum-drug incubation assay,immunohistochemistry and western blot were conducted.Hematoxylin-eosin staining showed that DG pre-treatment prevented Con A-induced liver structural damage in ICR mice.We also observed the reduced serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activities.However,the serum-drug incubation assay indicated that DG cannot directly attenuate ALT and AST levels.Meanwhile,experimental results proved that DG pretreatment down-regulates cleaved Caspase-3,cleaved PARP,ratio of BAX/BCL-2expression level and expression of TGF-β1,COX-2,IL-6,TNF-α,IFN-γinflammatory mediators.Taken together,DG can inhibit Con A-induced hepatic injury by inhibition of apoptosis and inflammation.