白细胞介素13对胆管成纤维细胞TGF-β1/Smads通路表达的影响及地塞米松的干预作用
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李克跃, Email: keyuelee@sohu.com

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贵州省科学技术厅—贵州省人民医院联合基金资助项目(黔科合LH字[2016]7146)。


Influence of interleukin 13 on activity of TGF-β1/Smads signaling pathway in bile duct fibroblasts and the interventional effect of dexamethasone
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    摘要:

    目的:探讨白细胞介素13(IL-13)对胆管成纤维细胞转化生长因子β1(TGF-β1)/Smads通路活性的影响及地塞米松(Dex)的干预作用。 方法:分离、培养兔胆管成纤维细胞并鉴定后分别给予IL-13、IL-13联合不同浓度的Dex(0.01、0.05、 0.25 mg/mL)干预48 h,以无处理的胆管成纤维细胞为空白对照,分别用CCK-8细胞计数法测定各组细胞增殖水平;real-time PCR检测各组细胞TGF-β1、Smad3及Smad4基因mRNA表达;Western blot检测各组细胞TGF-β1及Smad4蛋白表达。 结果:与空白对照组比较,在IL-13干预48 h后,胆管成纤维细胞增殖明显加速、TGF-β1、Smad3及Smad4 mRNA表达均明显上调,TGF-β1、Smad4蛋白表达明显上调(均P<0.05),而Dex对IL-13引起的上述变化有明显的抑制作用,并呈一定的浓度依赖趋势(部分P<0.05)。 结论:IL-13能增加胆管成纤维细胞TGF-β1/Smads通路的活性,削弱该通路的活化可能是Dex抑制良性胆道狭窄形成的机制之一。

    Abstract:

    Objective: To investigate the influence of interleukin 13 (IL-13) on activity of transforming growth factor-β1 (TGF-β1)/Smads signaling pathway in bile duct fibroblasts and the interventional effect of dexamethasone (Dex). Methods: Rabbit bile duct fibroblasts were isolated and cultured and then identified. Then, the bile duct fibroblasts were exposed to IL-13 or IL-13 plus different concentrations (0.01, 0.05 and 0.25 mg/mL) of Dex respectively for 48 h, using untreated bile duct fibroblasts as blank control. Afterwards, cell proliferation was assessed by CCK-8, the mRNA expressions of TGF-β1, Smad3 and Smad4 were determined by real-time PCR and the protein expressions of TGF-β1 and Smad4 were examined by Western blot. Results: In bile duct fibroblasts after exposure to IL-13 for 48 h, the cell proliferation was significantly increased, the mRNA expressions of TGF-β1, Smad3 and Smad4 and the protein expressions of TGF-β1 and Smad4 were significantly up-regulated (all P<0.05), and the above changes exerted by IL-13 were significantly inhibited by Dex addition in a certain concentration-dependent manner (part P<0.05). Conclusion: IL-13 can enhance the activity of TGF-β1/Smads pathway in bile duct fibroblasts, and weakening the activation of this signaling pathway may be one of the mechanisms of the inhibitory effect of Dex on benign biliary stricture.

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李克跃|石承先|汤可立|魏国微|刘振华|黎涛|张帅民|徐贤刚.白细胞介素13对胆管成纤维细胞TGF-β1/Smads通路表达的影响及地塞米松的干预作用[J].中国普通外科杂志,2017,26(8):987-992.
DOI:10.3978/j. issn.1005-6947.2017.08.006

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  • 收稿日期:2017-03-23
  • 最后修改日期:2017-07-13
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  • 在线发布日期: 2017-08-15