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黄芪甲苷通过调节TGF-1/Smad信号通路抑制肝纤维化。

Astragaloside Inhibits Hepatic Fibrosis by Modulation of TGF-1/Smad Signaling Pathway.

作者信息

Yuan Xingxing, Gong Zhiqiang, Wang Bingyu, Guo Xueying, Yang Lei, Li Dandan, Zhang Yali

机构信息

Department of Gastroenterology, Nangang Branch, Heilongjiang Academy of Traditional Chinese Medicine, No. 33 West Dazhi Road, Nangang District, Harbin, Heilongjiang 150006, China.

School of Pharmacy, Faculty of Chinese Medicine Science, Guangxi University of Chinese Medicine, No. 13 Wuhe Road, Qingxiu District, Nanning, Guangxi 530222, China.

出版信息

Evid Based Complement Alternat Med. 2018 Apr 30;2018:3231647. doi: 10.1155/2018/3231647. eCollection 2018.

Abstract

Activation of HSC is a pivotal step in hepatic fibrosis. In the activation of HSC, the TGF-1 plays a key role that can promote the occurrence of hepatic fibrosis by combining with Smad proteins. Astragaloside is the main active component extracted from that has the effect of antioxidation and hepatoprotection. In the present study, we investigated the mechanism of astragalosides inhibiting hepatic fibrosis and . , astragalosides inhibited the activation of HSC and regulated the expression of MMP-2 and TIMP-2 and reduced the formation of collagen fibers. , administration of astragalosides decreased the serum ALT, AST, and TBiL in rats by reducing oxidative stress. Astragalosides also attenuated hepatic fibrosis by reducing the concentration of hydroxyproline and inhibiting the formation of collagen fibers. The expressions of TGF-1, TR-I, p-Smad 2, and p-Smad 3 were downregulated after astragalosides treatments, while Smad 7 was upregulated compared to the control group. The results indicated that the effect of astragaloside on hepatic fibrosis was related to the inhibition of HSC activation and the modulation of the TGF-1/Smad signaling pathway.

摘要

肝星状细胞(HSC)的激活是肝纤维化的关键步骤。在HSC激活过程中,转化生长因子-β1(TGF-β1)发挥关键作用,它可通过与Smad蛋白结合促进肝纤维化的发生。黄芪甲苷是从黄芪中提取的主要活性成分,具有抗氧化和保肝作用。在本研究中,我们探究了黄芪甲苷抑制肝纤维化的机制,结果表明,黄芪甲苷抑制HSC激活,调节基质金属蛋白酶-2(MMP-2)和金属蛋白酶组织抑制因子-2(TIMP-2)的表达,并减少胶原纤维的形成。此外,黄芪甲苷给药可通过减轻氧化应激降低大鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)和总胆红素(TBiL)水平。黄芪甲苷还可通过降低羟脯氨酸浓度和抑制胶原纤维形成减轻肝纤维化。黄芪甲苷处理后,TGF-β1、I型转化生长因子受体(TR-I)、磷酸化Smad 2和磷酸化Smad 3的表达下调,而Smad 7与对照组相比上调。结果表明,黄芪甲苷对肝纤维化的作用与抑制HSC激活及调节TGF-β1/Smad信号通路有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6efa/5952439/4b032b095736/ECAM2018-3231647.001.jpg

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