Li Xiuqing, Zhang Hui, Pan Lijuan, Zou Haiou, Miao Xiaonan, Cheng Jing, Wu Youshan
Department of Gastroenterology and Hepatology, Lianyungang Oriental Hospital, Lianyungang, Jiangsu 222042, P.R. China.
Department of Gastroenterology and Hepatology, The Second Hospital of Lianyungang, Lianyungang, Jiangsu 222023, P.R. China.
Exp Ther Med. 2019 Jul;18(1):133-138. doi: 10.3892/etm.2019.7534. Epub 2019 Apr 30.
Liver fibrosis is a complex pathological process and an early step in the progression of liver cirrhosis, which can eventually develop into hepatocellular carcinoma. Currently, there is no effective treatment for liver fibrosis. Puerarin is a traditional Chinese herb, which is commonly used in the treatment of various diseases. In addition, it is also believed to have a therapeutic effect in liver fibrosis. However, whether puerarin reduces liver fibrosis via the ERK1/2 signaling pathway to inhibit the activation of hepatic stellate cell (HSC) and excessive collagen deposition in liver fibrosis remains unknown. The aim of the current study was to establish a liver fibrosis model by intraperitoneal injection of thioacetamide (TAA) and investigate the effect of puerarin in the treatment of liver fibrosis. Hematoxylin and eosin and Van Gieson's staining were used to examine histopathological changes associated with liver fibrosis. Liver hydroxyproline content was examined to determine the total amount of collagen in the liver. The relative protein expression levels of transforming growth factor β1 (TGFβ1), α-smooth muscle actin (α-SMA), collagen type I, fibronectin, ERK1/2 and p-ERK1/2 were determined by western blot analysis. In the TAA group, histopathological changes and collagen fiber content in rat liver tissue samples were significantly increased compared with the control group (P<0.05). In addition, treatment with puerarin significantly decreased histopathological changes and collagen fiber content in rat liver tissue samples (P<0.05). The relative protein expression levels of TGFβ1, α-SMA, collagen type I, fibronectin and p-ERK1/2 were significantly upregulated in the TAA group compared with the control group (P<0.05), whereas puerarin treatment reversed these changes. These findings suggest that treatment with puerarin may reduce HSC activation and alleviate extracellular matrix protein expression levels by inhibiting the TGF-β/ERK1/2 pathway in liver fibrosis.
肝纤维化是一个复杂的病理过程，是肝硬化进展的早期阶段，最终可发展为肝细胞癌。目前，肝纤维化尚无有效的治疗方法。葛根素是一种传统中药，常用于治疗各种疾病。此外，人们还认为它对肝纤维化有治疗作用。然而，葛根素是否通过细胞外信号调节激酶1/2（ERK1/2）信号通路减少肝纤维化，从而抑制肝星状细胞（HSC）的激活和肝纤维化中过多的胶原沉积，仍不清楚。本研究的目的是通过腹腔注射硫代乙酰胺（TAA）建立肝纤维化模型，并研究葛根素在治疗肝纤维化中的作用。采用苏木精-伊红染色和范吉森染色检查与肝纤维化相关的组织病理学变化。检测肝脏羟脯氨酸含量以确定肝脏中胶原的总量。通过蛋白质印迹分析测定转化生长因子β1（TGFβ1）、α-平滑肌肌动蛋白（α-SMA）Ⅰ型胶原、纤连蛋白、ERK1/2和磷酸化ERK1/2的相对蛋白表达水平。与对照组相比，TAA组大鼠肝组织样本的组织病理学变化和胶原纤维含量显著增加（P<0.05）。此外，葛根素治疗显著降低了大鼠肝组织样本的组织病理学变化和胶原纤维含量（P<0.05）。与对照组相比，TAA组中TGFβ1、α-SMA、Ⅰ型胶原、纤连蛋白和磷酸化ERK1/2的相对蛋白表达水平显著上调（P<0.05），而葛根素治疗逆转了这些变化。这些结果表明，葛根素治疗可能通过抑制肝纤维化中的TGF-β/ERK1/2途径减少HSC激活并减轻细胞外基质蛋白表达水平。
