Emodin alleviates CCl4‑induced liver fibrosis by suppressing epithelial‑mesenchymal transition and transforming growth factor‑β1 in rats.
Emodin alleviates CCl4‑induced liver fibrosis by suppressing epithelial‑mesenchymal transition and transforming growth factor‑β1 in rats.
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DOI：
10.3892/mmr.2018.9324
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发表时间：
2018-09
影响因子：
3.4
通讯作者：
Ma Z
中科院分区：
文献类型：
--
作者：
Liu F;Zhang J;Qian J;Wu G;Ma Z
肝纤维化是一种慢性疾病，表现出复杂的病理生理过程。其特征在于细胞外基质的沉积。大黄素是从大黄中提取的有效成分，具有抗菌、免疫抑制和抗炎作用。本研究旨在探讨大黄素抗大鼠肝纤维化的作用机制。通过每周两次皮下注射给予CCl 4，持续12周，产生肝纤维化大鼠模型。大黄素或羧甲基纤维素钠（CMC）作为溶媒，每日灌胃给药。12周后，取血检测肝功能指标，HE染色观察肝纤维化程度，Masson染色观察胶原沉积情况。此外，收集蛋白质和RNA样品用于进一步分析。本研究结果显示，大黄素以剂量依赖的方式显著降低肝功能指数和胶原沉积水平。此外，大黄素还降低了转化生长因子-β1（TGF-β1）的表达和母亲对十二指肠麻痹同源物2/3的磷酸化水平，并抑制了CCl 4诱导的E-钙粘蛋白下调和间充质标记物纤连蛋白和波形蛋白的上调。大黄素处理组TGF-β1、Snail家族转录抑制因子（Snail）2、Snail、twist-related protein 1和锌指E-box-binding homeobox（ZEB）1和2 mRNA的表达水平较对照组显著降低。本研究结果提示大黄素可能通过抑制TGF-β1信号通路和上皮-间质转化发挥抗纤维化作用。
Liver fibrosis is a chronic disease that exhibits a complicated pathophysiology. It is characterized by the deposition of the extracellular matrix. Emodin, an active constituent isolated from rhubarb, has antibacterial, immunosuppressive and anti-inflammatory effects. In the present study, the mechanism through which emodin alleviates liver fibrosis in rats was investigated. A rat model of liver fibrosis was generated by administering CCl4 via subcutaneous injection twice a week for 12 weeks. Emodin or sodium carboxymethylcellulose (CMC), as the vehicle, were intragastrically administered daily. After 12 weeks, the liver function index was examined by blood analysis, histopathological scores of fibrosis was determined by hematoxylin and eosin staining and level of collagen deposition was examined by Masson staining. In addition, protein and RNA samples were collected for further analysis. The results of the present study revealed that emodin significantly reduced the liver function index and level of collagen deposition in a dose-dependent manner. Furthermore, emodin reduced the expression of transforming growth factor-β1 (TGF-β1) and the phosphorylation levels of mothers against decapentaplegic homolog 2/3, and inhibited the CCl4-induced downregulation of E-cadherin and upregulation of the mesenchymal markers, fibronectin and vimentin. The expression levels of TGF-β1, Snail family transcriptional repressor (Snail) 2, Snail, twist-related protein 1 and zinc finger E-box-binding homeobox (ZEB)1 and 2 mRNA were significantly decreased in emodin-treated groups compared with the untreated control. Collectively, the results of the present study suggested that emodin may exert antifibrotic effects via the suppression of TGF-β1 signaling and epithelial-mesenchymal transition.
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DOI：
10.1007/978-3-319-41334-1_3
发表时间：
2016-01-01
期刊：
ANTI-INFLAMMATORY NUTRACEUTICALS AND CHRONIC DISEASES
影响因子：
--
作者：
Monisha, B. Anu;Kumar, Niraj;Tiku, Ashu Bhan
通讯作者：
Tiku, Ashu Bhan
大黄素通过抑制上皮间质转化和成纤维细胞活化改善博莱霉素诱导的大鼠肺纤维化
影响因子：
4.6
作者：
Guan R;Wang X;Zhao X;Song N;Zhu J;Wang J;Wang J;Xia C;Chen Y;Zhu D;Shen L
通讯作者：
Shen L
大黄素和厄贝沙坦对高血压大鼠心室纤维化的影响
影响因子：
1.6
作者：
Chen, Qiang;Pang, Lingpin;Huang, Dangsheng
通讯作者：
Huang, Dangsheng
影响因子：
6
作者：
Hu, Biao;Gharaee-Kermani, Mehrnaz;Phan, Sem H.
通讯作者：
Phan, Sem H.
大黄素减轻博莱霉素诱导的大鼠肺纤维化
影响因子：
3.5
作者：
Guan, Ruijuan;Zhao, Xiaomei;Shen, Linlin
通讯作者：
Shen, Linlin