Zhou Bu-Gao, Zhao Hai-Mei, Lu Xiu-Yun, Wang Xin, Zou Yong, Xu Rong, Yue Hai-Yang, Liu Yi, Zuo Zheng-Yun, Liu Duan-Yong
Science and Technology College, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi Province 330004, China.
School of Basic Medical Sciences, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi Province 330004, China.
Evid Based Complement Alternat Med. 2017;2017:5653643. doi: 10.1155/2017/5653643. Epub 2017 May 30.
The present study aimed to investigate the mechanism of hepatoprotective effect of Erzhi Pill (EZP) on the liver injury via observing TSC/mTOR signaling pathway activation. The experimental liver injury was induced by 2-acetylaminofluorene (2-AAF) treatment combined with partial hepatectomy (PH). EZP treated 2-AAF/PH-induced liver injury by the therapeutic and prophylactic administration. After the administration of EZP, the activities of aspartic transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AKP), and gamma-glutamyl transpeptidase (-GT) were decreased, followed by the decreased levels of hepatocyte apoptosis and caspase-3 expression. However, the secretion of albumin, liver weight, and index of liver weight were elevated. Microscopic examination showed that EZP restored pathological liver injury. Meanwhile, Rheb and mammalian target of rapamycin (mTOR) activation were suppressed, and tuberous sclerosis complex (TSC) expression was elevated in liver tissues induced by 2-AAF/PHx and accompanied with lower-expression of Bax, Notch1, p70S6K, and 4E-EIF and upregulated levels of Bcl-2 and Cyclin D. Hepatoprotective effect of EZP was possibly realized via inhibiting TSC/mTOR signaling pathway to suppress excessive apoptosis of hepatocyte.
本研究旨在通过观察结节性硬化症复合物(TSC)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路的激活情况,探讨二至丸(EZP)对肝损伤的肝保护作用机制。实验性肝损伤通过给予2-乙酰氨基芴(2-AAF)并结合部分肝切除术(PH)诱导。EZP通过治疗性给药和预防性给药来处理2-AAF/PH诱导的肝损伤。给予EZP后,天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、碱性磷酸酶(AKP)和γ-谷氨酰转肽酶(-GT)的活性降低,随后肝细胞凋亡水平和半胱天冬酶-3表达降低。然而,白蛋白分泌、肝脏重量和肝脏重量指数升高。显微镜检查显示EZP可恢复肝脏病理损伤。同时,在2-AAF/PHx诱导的肝组织中,小G蛋白Rheb和雷帕霉素哺乳动物靶蛋白(mTOR)的激活受到抑制,结节性硬化症复合物(TSC)表达升高,并伴有Bax、Notch1、p70S6K和4E-EIF的低表达以及Bcl-2和细胞周期蛋白D水平的上调。EZP的肝保护作用可能是通过抑制TSC/mTOR信号通路来抑制肝细胞的过度凋亡而实现的。