本文選題：Hepatic　切入點：stellate　出處：《延邊大學》2014年碩士論文　論文類型：學位論文

【摘要】：目的與背景：ATP介導的P2X7受體在肝纖維化的治療過程當中,是一種新型的治療靶點。現(xiàn)今研究發(fā)現(xiàn)脂多糖LPS和促炎因子的作用可以與之相關,但是其潛在機制尚不了解。 方法：我們將實驗分組一組運用巨噬細胞經(jīng)過LPS刺激24h后得到了的上清液作用于人星狀細胞中,與另一組LPS直接作用于人星狀細胞比較各種細胞因子mRNA的表達差異；后續(xù)實驗在上述的對照條件下LPS改為刺激4h,在收集的前30min時加入能夠協(xié)同P2X7受體發(fā)揮作用的ATP,以及P2X7受體的抑制劑A438079,通過比較細胞因子mRNA表達差異來研究這些因素對星狀細胞激活的作用；最后,通過蛋白印跡分析在經(jīng)過LPS刺激后的星狀細胞中的P2X7受體的激活對于IL-β前體成熟的促進作用。 結果：用經(jīng)過LPS刺激過24h的巨噬細胞的上清液作用于星狀細胞相比直接加入LPS刺激24h星狀細胞的組,纖維化相關的各項指標α-SMA、collagen-I、IL-1β IL-18、IL-6以及P2X7r等的mRNA表達提高；經(jīng)過LPS刺激過4h的星狀細胞中,ATP相關的P2X7r也可以促進上述指標的表達,該受體的抑制劑A438079可以降低細胞因子的表達水平；在對于IL-1p的蛋白分析結果可以看出P2X7受體的激活可以催化IL-1β前體的成熟。 結論：實驗證明,巨噬細胞在一定程度上可以促進肝星狀細胞的激活；ATP相關的P2X7r對于星狀細胞激活,對炎癥反應的發(fā)生均起到促進作用。其研究可以在未來通過受體治療肝纖維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 偽 -SMAcollagen-I 尾 IL-18IL-6, P2X7r and 偽 -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 偽 -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.
【學位授予單位】：延邊大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R575

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本文編號：1559960