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中药复方861通过上调胆管结扎模型大鼠的BMP-7/Smad信号通路减轻肝纤维化

Attenuation of liver fibrosis by herbal compound 861 via upregulation of BMP-7/Smad signaling in the bile duct ligation model rat.

作者信息

Hou Fei, Liu Ruixia, Liu Xiaoya, Cui Lijian, Wen Yan, Yan Songbiao, Yin Chenghong

机构信息

Department of Infection, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.

Department of Internal Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, P.R. China.

出版信息

Mol Med Rep. 2016 May;13(5):4335-42. doi: 10.3892/mmr.2016.5071. Epub 2016 Mar 30.

Abstract

Herbal compound 861 (Cpd 861) exerts an anti-fibrotic effect in patients with hepatic fibrosis; however, the anti-fibrotic mechanism has yet to be fully elucidated. The present study aimed to explore the mechanistic basis for the anti-fibrotic effect, with a focus on bone morphogenetic protein 7 (BMP-7)/Smad signaling in a bile duct ligation (BDL)-induced liver fibrosis rat model. Following the induction of hepatic fibrosis, rats induced by BDL were treated with 9 g/kg Cpd 861 daily or an equal volume of saline for 28 days. Serum samples were prepared for monitoring the levels of alanine transaminase, aspartate transaminase and total bilirubin, and direct bilirubin analyses and liver samples were used to investigate gene expression, protein localization and protein expression analysis using real‑time quantitative polymerase chain reaction, immunohistochemistry and western blotting. The results revealed the attenuation of liver fibrosis by Cpd 861 in the histological and biochemical experiments. BMP‑7 and phospho (p)‑Smad1/5/8 were localized predominantly in the cytoplasm of hepatocytes. In comparison with the saline‑treated BDL rats, Cpd 861 markedly upregulated the gene expression of BMP‑7 and Smad5, as well as the protein expression of BMP‑7 and Smad1/5. In addition, p-Smad1/5/8 protein expression was markedly increased by Cpd 861 in the BDL model. These results indicated that Cpd 861 alleviates hepatic fibrosis possibly via the upregulation and activation of BMP-7/Smad signaling in hepatic fibrotic rats.

摘要

中药复方861(Cpd 861)对肝纤维化患者具有抗纤维化作用;然而,其抗纤维化机制尚未完全阐明。本研究旨在探讨抗纤维化作用的机制基础,重点关注胆管结扎(BDL)诱导的肝纤维化大鼠模型中的骨形态发生蛋白7(BMP - 7)/Smad信号通路。诱导肝纤维化后,BDL诱导的大鼠每天用9 g/kg Cpd 861或等体积生理盐水治疗28天。制备血清样本以监测丙氨酸转氨酶、天冬氨酸转氨酶和总胆红素水平,并进行直接胆红素分析,同时使用肝脏样本通过实时定量聚合酶链反应、免疫组织化学和蛋白质印迹法研究基因表达、蛋白质定位和蛋白质表达分析。结果在组织学和生化实验中显示Cpd 861可减轻肝纤维化。BMP - 7和磷酸化(p)-Smad1/5/8主要定位于肝细胞的细胞质中。与生理盐水处理的BDL大鼠相比,Cpd 861显著上调BMP - 7和Smad5的基因表达以及BMP - 7和Smad1/5的蛋白质表达。此外,在BDL模型中Cpd 861使p - Smad1/5/8蛋白质表达显著增加。这些结果表明,Cpd 861可能通过上调和激活肝纤维化大鼠中的BMP - 7/Smad信号通路来减轻肝纤维化。

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