Zhao Hai-Mei, Zhang Xiao-Yun, Lu Xiu-Yun, Yu Song-Ren, Wang Xin, Zou Yong, Zuo Zheng-Yun, Liu Duan-Yong, Zhou Bu-Gao
School of Basic Medical Sciences, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
Department of Postgraduate, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
Front Pharmacol. 2018 Mar 27;9:283. doi: 10.3389/fphar.2018.00283. eCollection 2018.
Erzhi Pill (EZP) is one of the basic prescriptions for treating liver diseases in traditional Chinese medicine. However, its mechanism of action is still undefined. The PI3K/AKT/Raptor/Rictor signaling pathway is closely related to apoptosis and plays a significant role in the pathogenesis of liver disease. To define the mechanism of the hepatoprotective effect of EZP in the treatment of liver disease, hepatic injury induced by 2-acetylaminofluorene/partial hepatectomy was treated by EZP for 14 days. The therapeutic effect of EZP was confirmed by the decreased production of aspartate aminotransferase and alanine aminotransferase, recovery of pathological liver injury, followed by inhibition of pro-inflammatory cytokines and transforming growth factor-β1. Bromodeoxyuridine assay and TUNEL staining indicated that apoptosis was suppressed and the numbers of cells in S phase and G0/G1phase were decreased. The crucial proteins in the PI3K/AKT/Raptor/Rictor signaling pathway were deactivated in rats with experimental liver injury treated by EZP. These results indicated that the hepatoprotective effect of EZP via inhibition of hepatocyte apoptosis was closely related to repression of the PI3K/Akt/Raptor/Rictor signaling pathway.
二至丸(EZP)是中医治疗肝脏疾病的基本方剂之一。然而,其作用机制仍不明确。PI3K/AKT/Raptor/Rictor信号通路与细胞凋亡密切相关,在肝脏疾病的发病机制中起重要作用。为明确二至丸在治疗肝脏疾病中保肝作用的机制,采用2-乙酰氨基芴/部分肝切除术诱导肝损伤,并用二至丸治疗14天。二至丸的治疗效果通过天冬氨酸转氨酶和丙氨酸转氨酶生成减少、肝脏病理损伤恢复、促炎细胞因子和转化生长因子-β1受抑制得以证实。溴脱氧尿苷检测和TUNEL染色表明细胞凋亡受到抑制,S期和G0/G1期细胞数量减少。在接受二至丸治疗的实验性肝损伤大鼠中,PI3K/AKT/Raptor/Rictor信号通路中的关键蛋白失活。这些结果表明,二至丸通过抑制肝细胞凋亡产生的保肝作用与PI3K/Akt/Raptor/Rictor信号通路的抑制密切相关。