Guan Cui-wen, Jin Jing, Li Jia, Zhao Zhong-xiang, Huang Zhi-ying
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Yao Xue Xue Bao. 2013 Sep;48(9):1397-402.
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 x 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.
本研究旨在探讨丹参酮IIA（Tan）对雷公藤内酯醇（TP）诱导的肝损伤的保护作用及其相关机制。通过腹腔注射TP（1mg·kg⁻¹）诱导小鼠急性肝损伤。检测血清中AST、ALT和LDH的活性以及肝组织中GSH、GST、GSH-PX、SOD、CAT和MDA的水平。HE染色后观察肝组织的组织病理学变化。通过蛋白质免疫印迹法检测肝组织中Nrf2的易位，并用实时PCR法测定GCLC、NQO1和HO-1 mRNA的表达水平。结果表明，Tan预处理可显著减轻TP诱导的肝损伤，表现为AST、ALT和LDH活性降低（P<0.01）。Tan预处理还通过抑制MDA并恢复GSH、GST、SOD和CAT水平来预防TP诱导的小鼠肝脏氧化应激（P<0.05）。与这些变化平行，Tan预处理可减轻TP诱导的组织病理学变化。此外，结果表明，Tan预处理导致Nrf2核积累以及抗氧化反应元件（ARE）驱动基因如GCLC、NQO1和HO-1的mRNA表达诱导。这些结果表明，Tan可通过激活Nrf2/ARE途径保护免受TP诱导的急性肝损伤。
