丹参酮ⅡA激活Nrf2/ARE通路保护雷公藤甲素所致急性肝损伤  

Tanshinone ⅡA protects against triptolide-induced liver injury via Nrf2/ARE activation

作　　者：关翠雯[1] 金晶[1] 李佳[1] 赵钟祥[2] 黄芝瑛[1] 

机构地区：[1]中山大学药学院,广东广州510006 [2]广州中医药大学中药学院,广东广州510006

出　　处：《药学学报》2013年第9期1397-1402,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81102886)

摘　　要：研究丹参酮ⅡA(tanshinone ⅡA,Tan)对雷公藤甲素(triptolide,TP)所致小鼠急性肝损伤的保护作用及相关机制。腹腔注射TP(1 mg·kg-1)建立小鼠急性肝损伤模型。检测血清中AST、ALT和LDH活性,测定肝组织中GSH、GST、GSH-PX、SOD、CAT和MDA含量,HE染色观察肝组织病理改变,Western blotting检测肝组织细胞核内Nrf2的表达,实时定量PCR检测肝组织GCLC、NQO1和HO-1 mRNA表达水平。结果显示,与TP组比较,Tan保护组(10和30 mg·kg 1)血清AST、ALT和LDH活性明显降低,肝组织GSH、GST、SOD及CAT明显升高,而MDA明显降低,肝组织病理改变也明显减轻。同时Tan保护组能显著诱导肝组织中的Nrf2转位入核,其下游靶基因GCLC、NQO1和HO-1 mRNA表达水平也显著升高。研究表明,Tan对TP所致急性肝损伤有保护作用,其机制与激活Nrf2/ARE通路有关。The aim of this study is to investigate the protection effect of tanshinone IIA （Tan） against triptolide （TP）-induced liver injury and the mechanisms involved. Acute liver injury was induced by intraperitoneal injection of TP （1 mg·kg^-1） in mice. The activities of AST, ALT and LDH in serum and the levels of GSH, GST, GSH-PX, SOD, CAT and MDA in liver tissue were detected. The histopathological changes of liver tissues were observed after HE staining. Nrf2 translocation in liver tissue was detected by Western blotting, and real-time PCR was used to measure the expression levels of GCLC, NQO1 and HO-1 mRNA. The results showed that pretreatment with Tan significantly prevented the TP induced liver injury as indicated by reducing the activities of AST, ALT and LDH （P 〈 0.01）. Tan pretreatment also prevented TP-induced oxidative stress in the mice liver by inhibiting MDA and restoring the levels of GSH, GST, SOD and CAT （P 〈 0.05）. Parallel to these changes, pretreatment with Tan could attenuate histopathologic changes induced by TP. Furthermore, the results indicated that Tan pretreatment caused nuclear accumulation of Nrf2 as well as induction of mRNA expression of antioxidant response element （ARE）-driven genes such as GCLC, NQO1 and HO-1. These results indicated that Tan could protect against TP-induced acute liver injury via the activation of Nrf2/ARE pathway.

关 键 词：丹参酮ⅡA 雷公藤甲素 NRF2 ARE通路 肝损伤 

分 类 号：R965[医药卫生—药理学]