Li Shu, Zhao Wei, Tao Yanyan, Liu Chenghai
Department of Gastroenterology, Baoshan Branch, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai 201900, China.
Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai 201203, China.
Am J Transl Res. 2020 Feb 15;12(2):592-601. eCollection 2020.
Hepatic fibrosis is a repair and healing reaction for chronic injuries of liver. This study aimed to investigate protective effects of Fugan Wan (FGW) on hepatic fibrosis and clarify associated mechanisms. Hepatic fibrosis model was established by administrating dimethyl nitrosamine (DMN) to rats. Rats were divided into control, DMN and FGW groups. Haematoxylin and eosin (HE) staining was conducted to evaluate inflammatory response in hepatic fibrosis tissues. Sirius red staining was used to assess collagen disposition. Quantitative real-time PCR (qRT-PCR) was employed to detect antiotensin-converting enzyme homologue 2 (ACE2), Mas, transforming growth factor β1 (TGF-β1) mRNA. Western blot was used to examine collagen I, smooth muscle actin α (α-SMA), angiotensin type 1 receptor (AT-1R), extra-cellular regulated protein kinase (ERK), phosphorylated ERK (p-ERK), c-Jun and phosphorylated-c-Jun (p-c-Jun) expression. The results indicated that FGW significantly reduced inflammatory response of hepatic fibrosis tissues. FGW significantly decreased collagen deposition compared to that of DMN group ( < 0.01). FGW significantly down-regulated α-SMA expression compared to that of DMN group ( < 0.01). FGW significantly decreased AT-1R levels compared to that of DMN group ( < 0.01). Comparing with DMN group, ACE2 and Mas mRNA levels were significantly increased in FGW group ( < 0.01). FGW significantly down-regulated p-c-Jun and p-ERK1/2 compared to DMN group ( < 0.01). GFW significantly inhibited compared to DMN group ( < 0.01). In conclusion, FGW alleviated hepatic fibrosis by inhibiting ACE/Ang II/AT-1R signaling and enhancing ACE2/Ang 1-7/Mas signaling pathway in hepatic fibrosis rat models.
肝纤维化是肝脏慢性损伤的一种修复和愈合反应。本研究旨在探讨复肝丸（FGW）对肝纤维化的保护作用并阐明相关机制。通过给大鼠腹腔注射二甲基亚硝胺（DMN）建立肝纤维化模型。将大鼠分为对照组、DMN组和FGW组。采用苏木精-伊红（HE）染色评估肝纤维化组织中的炎症反应。用天狼星红染色评估胶原分布。采用定量实时聚合酶链反应（qRT-PCR）检测血管紧张素转换酶同源物2（ACE2）、Mas、转化生长因子β1（TGF-β1）的mRNA。采用蛋白质免疫印迹法检测Ⅰ型胶原、平滑肌肌动蛋白α（α-SMA）、血管紧张素1型受体（AT-1R）、细胞外调节蛋白激酶（ERK）、磷酸化ERK（p-ERK）、c-Jun和磷酸化c-Jun（p-c-Jun）的表达。结果表明，FGW显著降低了肝纤维化组织的炎症反应。与DMN组相比，FGW显著减少了胶原沉积（<0.01）。与DMN组相比，FGW显著下调了α-SMA的表达（<0.01）。与DMN组相比，FGW显著降低了AT-IR水平（<0.01）。与DMN组相比，FGW组的ACE2和Mas mRNA水平显著升高（<0.01）。与DMN组相比，FGW显著下调了p-c-Jun和p-ERK1/2（<0.叭）。与DMN组相比，GFW显著抑制（<0.01）（此处原文可能有误，推测是FGW）。总之，在肝纤维化大鼠模型中，FGW通过抑制ACE/Ang II/AT-1R信号通路和增强ACE2/Ang 1-7/Mas信号通路减轻肝纤维化。
