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A Compound of Chinese Herbs Protects against Alcoholic Liver Fibrosis in Rats via the TGF-β1/Smad Signaling Pathway

机译:一种中草药化合物通过TGF-β1/ Smad信号通路保护大鼠抗酒精性肝纤维化

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摘要

Alcoholic liver fibrosis (ALF) has become a major public health concern owing to its health impacts and the lack of effective treatment strategies for the disease. In this study, we investigated the effect of a compound composed of Chinese herbs Pueraria lobata (Willd.), Salvia miltiorrhiza, Schisandra chinensis, and Silybum marianum on ALF. An ALF model was established. Rats were fed with modified Lieber–Decarli alcohol liquid diet and injected with trace CCl4 at late stage. The rats were then treated with several doses of the compound. Biochemical and fibrosis-relevant parameters were measured from the sera obtained from the rats. Liver tissues were obtained for hematoxylin and eosin and Masson's trichrome staining. Matrix metalloproteinase-13 and tissue inhibitor of metalloproteinase-1 were determined by immunohistochemistry assays. The mRNA and protein expression levels of transforming growth factor-β1 (TGF-β1), Smad2, Smad3, and Smad7 on the livers were also measured by quantitative polymerase chain reaction and Western blot. Results showed that the compound treatment alleviated pathological lesions in the liver, decreased the serum levels of hyaluronan, laminin, and hydroxyproline, and diminished the expression of hepatic tissue inhibitor of metalloproteinase-1. Compound treatment also increased hepatic matrix metalloproteinase-13 expression and inhibited the TGF-β1/Smad signaling pathway. In conclusion, the compound has a protective effect against ALF in rats, and an underlying mechanism is involved in the TGF-β1/Smad signaling pathway.
机译:酒精性肝纤维化(ALF)由于其对健康的影响以及缺乏对该疾病的有效治疗策略,已成为主要的公共卫生问题。在这项研究中,我们调查了由中药葛根,丹参,五味子和马来草组成的化合物对ALF的影响。建立了ALF模型。给大鼠喂食改良的Lieber-Decarli酒精流质饮食,并在后期注射微量CCl4。然后用几种剂量的化合物治疗大鼠。从从大鼠获得的血清中测量与生化和纤维化相关的参数。获得肝组织用于苏木精和曙红和Masson三色染色。通过免疫组织化学测定确定基质金属蛋白酶-13和金属蛋白酶-1的组织抑制剂。还通过定量聚合酶链反应和蛋白质印迹法测定了肝脏中转化生长因子-β1(TGF-β1),Smad2,Smad3和Smad7的mRNA和蛋白表达水平。结果表明,该化合物治疗减轻了肝脏的病理损伤,降低了透明质酸,层粘连蛋白和羟脯氨酸的血清水平,并减少了肝组织金属蛋白酶-1的表达。化合物治疗还增加了肝基质金属蛋白酶-13的表达并抑制了TGF-β1/ Smad信号通路。总之,该化合物具有抗大鼠ALF的保护作用,其潜在的机制与TGF-β1/ Smad信号通路有关。

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