来自远志的黄烷酮通过靶向TGF-β1/TβR/Smad信号通路抑制上皮-间质转化从而减轻四氯化碳诱导的大鼠肝纤维化。

Flavanones from Bunge Alleviate CCl-Induced Liver Fibrosis in Rats by Targeting TGF-1/TR/Smad Pathway In Turn Inhibiting Epithelial Mesenchymal Transition.

作者信息

Lin Yuancan, Luo Haiying, Wang Xiao, Zheng Minxia, Jin Qianxing, Chen Hongshu, Pan Peilei, Zhang Junjie

机构信息

The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China.

Hangzhou Sanatorium of People's Liberation Army, Hangzhou 310007, China.

出版信息

Evid Based Complement Alternat Med. 2018 Feb 15;2018:3080837. doi: 10.1155/2018/3080837. eCollection 2018.

DOI:10.1155/2018/3080837

PMID:29636774

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5832160/

Abstract

OBJECTIVE

The aim of the study is to evaluate the therapeutic effects of flavanones from Bunge (FSSB) on CCl-induced liver fibrosis in rats and the underlying mechanisms of action.

METHODS

An experimental model of liver fibrosis was established by subcutaneous injection of rats with CCl (40% v/v, 3 ml/kg) twice per week for six weeks. FSSB (100, 200, and 400 mg/kg) was intragastrically administered once per day consecutively for five weeks.

RESULTS

Our results showed that FSSB significantly attenuated CCl-induced liver fibrosis as evidenced by reducing the elevated levels of serum biochemical indexes and improving the histological changes, including decreasing the elevation in serum alanine transaminase (ALT), aspartate transaminase (AST), hyaluronic acid (HA), and laminin (LN) level, reducing infiltration of inflammatory cells and collagen fibers in liver tissue. In addition, compared to the model group, FSSB markedly downregulated the protein and mRNA expression of TGF-1, TGF-1 receptors I and II (TRI and TRII), Smad2, Smad3, and Vimentin in liver tissue, at the mean time upregulating the expression of Smad7 and E-cadherin.

CONCLUSIONS

The results suggest that FSSB alleviated CCl-induced liver fibrosis probably through inhibition of TGF-/TR/Smad pathway in turn inhibiting epithelial mesenchymal transition.

摘要

目的

本研究旨在评估光果葶苈子黄酮（FSSB）对四氯化碳诱导的大鼠肝纤维化的治疗效果及其潜在作用机制。

方法

通过每周两次皮下注射四氯化碳（40% v/v，3 ml/kg），连续六周建立大鼠肝纤维化实验模型。FSSB（100、200和400 mg/kg）连续五周每天灌胃一次。

结果

我们的结果表明，FSSB显著减轻了四氯化碳诱导的肝纤维化，这表现为血清生化指标升高水平降低以及组织学变化改善，包括血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、透明质酸（HA）和层粘连蛋白（LN）水平升高降低，肝组织中炎性细胞和胶原纤维浸润减少。此外，与模型组相比，FSSB显著下调肝组织中TGF-1、TGF-1受体I和II（TRI和TRII）、Smad2、Smad3和波形蛋白的蛋白和mRNA表达，同时上调Smad7和E-钙黏蛋白的表达。