Key Laboratory of Liver and Kidney Diseases Ministry of Education, Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
BMC Complement Altern Med. 2012 Apr 3;12:33. doi: 10.1186/1472-6882-12-33.
Huangqi decoction was first described in Prescriptions of the Bureau of Taiping People's Welfare Pharmacy in Song Dynasty (AD 1078), and it is an effective recipe that is usually used to treat consumptive disease, anorexia, and chronic liver diseases. Transforming growth factor beta 1 (TGFβ1) plays a key role in the progression of liver fibrosis, and Huangqi decoction and its ingredients (IHQD) markedly ameliorated hepatic fibrotic lesions induced by ligation of the common bile duct (BDL). However, the mechanism of IHQD on hepatic fibrotic lesions is not yet clear. The purpose of the present study is to elucidate the roles of TGFβ1 activation, Smad-signaling pathway, and extracellular signal-regulated kinase (ERK) in the pathogenesis of biliary fibrosis progression and the antifibrotic mechanism of IHQD.
A liver fibrosis model was induced by ligation of the common bile duct (BDL) in rats. Sham-operation was performed in control rats. The BDL rats were randomly divided into two groups: the BDL group and the IHQD group. IHQD was administrated intragastrically for 4 weeks. At the end of the fifth week after BDL, animals were sacrificed for sampling of blood serum and liver tissue. The effect of IHQD on the TGFβ1 signaling pathway was evaluated by western blotting and laser confocal microscopy.
Decreased content of hepatic hydroxyproline and improved liver function and histopathology were observed in IHQD rats. Hepatocytes, cholangiocytes, and myofibroblasts in the cholestatic liver injury released TGFβ1, and activated TGFβ1 receptors can accelerate liver fibrosis. IHQD markedly inhibited the protein expression of TGFβ1, TGFβ1 receptors, Smad3, and p-ERK1/2 expression with no change of Smad7 expression.
IHQD exert significant therapeutic effects on BDL-induced fibrosis in rats through inhibition of the activation of TGFβ1-Smad3 and TGFβ1-ERK1/2 signaling pathways.
黄芪汤最早记载于宋代（公元 1078 年）的《太平惠民和剂局方》，是一种常用于治疗虚劳、厌食和慢性肝病的有效方剂。转化生长因子-β1（TGFβ1）在肝纤维化的进展中起着关键作用，黄芪汤及其成分（IHQD）显著改善了胆总管结扎（BDL）诱导的肝纤维化病变。然而，IHQD 对肝纤维化病变的作用机制尚不清楚。本研究旨在阐明 TGFβ1 激活、Smad 信号通路和细胞外信号调节激酶（ERK）在胆管纤维化进展中的发病机制以及 IHQD 的抗纤维化机制。
采用胆总管结扎（BDL）法诱导大鼠肝纤维化模型。对照组大鼠行假手术。BDL 大鼠随机分为两组：BDL 组和 IHQD 组。IHQD 灌胃给药 4 周。BDL 后第 5 周末处死动物，取血清和肝组织样本。通过 Western blot 和激光共聚焦显微镜评估 IHQD 对 TGFβ1 信号通路的影响。
IHQD 组大鼠肝组织羟脯氨酸含量降低，肝功能和组织病理学改善。胆汁淤积性肝损伤的肝细胞、胆管细胞和肌成纤维细胞释放 TGFβ1，激活的 TGFβ1 受体可加速肝纤维化。IHQD 显著抑制 TGFβ1、TGFβ1 受体、Smad3 和 p-ERK1/2 蛋白表达，而 Smad7 表达无变化。
IHQD 通过抑制 TGFβ1-Smad3 和 TGFβ1-ERK1/2 信号通路的激活，对 BDL 诱导的大鼠肝纤维化具有显著的治疗作用。
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