P2X7受体抑制剂干预炎症介导的星状细胞的激活

发布时间：2018-03-03 06:51

  本文选题：Hepatic　切入点：stellate　出处：《延边大学》2014年硕士论文　论文类型：学位论文

【摘要】：目的与背景：ATP介导的P2X7受体在肝纤维化的治疗过程当中,是一种新型的治疗靶点。现今研究发现脂多糖LPS和促炎因子的作用可以与之相关,但是其潜在机制尚不了解。 方法：我们将实验分组一组运用巨噬细胞经过LPS刺激24h后得到了的上清液作用于人星状细胞中,与另一组LPS直接作用于人星状细胞比较各种细胞因子mRNA的表达差异；后续实验在上述的对照条件下LPS改为刺激4h,在收集的前30min时加入能够协同P2X7受体发挥作用的ATP,以及P2X7受体的抑制剂A438079,通过比较细胞因子mRNA表达差异来研究这些因素对星状细胞激活的作用；最后,通过蛋白印迹分析在经过LPS刺激后的星状细胞中的P2X7受体的激活对于IL-β前体成熟的促进作用。 结果：用经过LPS刺激过24h的巨噬细胞的上清液作用于星状细胞相比直接加入LPS刺激24h星状细胞的组,纤维化相关的各项指标α-SMA、collagen-I、IL-1β IL-18、IL-6以及P2X7r等的mRNA表达提高；经过LPS刺激过4h的星状细胞中,ATP相关的P2X7r也可以促进上述指标的表达,该受体的抑制剂A438079可以降低细胞因子的表达水平；在对于IL-1p的蛋白分析结果可以看出P2X7受体的激活可以催化IL-1β前体的成熟。 结论：实验证明,巨噬细胞在一定程度上可以促进肝星状细胞的激活；ATP相关的P2X7r对于星状细胞激活,对炎症反应的发生均起到促进作用。其研究可以在未来通过受体治疗肝纤维疾病化上起到一定作用。
[Abstract]:Objective and background P2X7 receptor mediated by ATP is a novel therapeutic target in the treatment of liver fibrosis. Now it has been found that the role of lipopolysaccharide (LPS) and proinflammatory factor can be associated with P2X7 receptor, but the underlying mechanism is not yet understood. Methods: one group of human stellate cells was treated with macrophage supernatant stimulated by LPS for 24 h. The expression of cytokines mRNA was compared with that of another group of LPS directly acting on human stellate cells. In the subsequent experiment, LPS was changed to stimulate for 4 h under the above control condition, and then added in the first 30 minutes of collection, which could work together with P2X7 receptor, and the inhibitor of P2X7 receptor, A438079. The difference of cytokine mRNA expression was compared to study these reasons. The action of stellate cells activated by stellate cells; Finally, the activation of P2X7 receptors in stellate cells stimulated by LPS was analyzed by Western blotting to promote the maturation of IL- 尾 precursors. Results: the expression of 伪 -SMAcollagen-I 尾 IL-18IL-6, P2X7r and 伪 -SMA-collagen-I was increased in the stellate cells treated with the supernatant of macrophages stimulated by LPS for 24 h. Compared with the control group stimulated by LPS directly for 24 h, the expression of 伪 -SMA-collagen-I 尾 IL-18IL-6 and P2X7r were increased. P2X7r, which was stimulated by LPS for 4 h, could also promote the expression of these markers. A438079, an inhibitor of the receptor, could decrease the expression of cytokines. The activation of P2X7 receptor can catalyze the maturation of IL-1 尾 precursor. Conclusion: macrophages can promote the activation of hepatic stellate cells by ATP related P2X7r to some extent. It can play a certain role in the treatment of liver fiber disease through the receptor in the future.
【学位授予单位】：延边大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R575

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