發(fā)布時(shí)間：2018-03-03 06:51

  本文選題：Hepatic　切入點(diǎn)：stellate　出處：《延邊大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：目的與背景：ATP介導(dǎo)的P2X7受體在肝纖維化的治療過(guò)程當(dāng)中,是一種新型的治療靶點(diǎn)。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(guān),但是其潛在機(jī)制尚不了解。 方法：我們將實(shí)驗(yàn)分組一組運(yùn)用巨噬細(xì)胞經(jīng)過(guò)LPS刺激24h后得到了的上清液作用于人星狀細(xì)胞中,與另一組LPS直接作用于人星狀細(xì)胞比較各種細(xì)胞因子mRNA的表達(dá)差異；后續(xù)實(shí)驗(yàn)在上述的對(duì)照條件下LPS改為刺激4h,在收集的前30min時(shí)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(guò)比較細(xì)胞因子mRNA表達(dá)差異來(lái)研究這些因素對(duì)星狀細(xì)胞激活的作用；最后,通過(guò)蛋白印跡分析在經(jīng)過(guò)LPS刺激后的星狀細(xì)胞中的P2X7受體的激活對(duì)于IL-β前體成熟的促進(jìn)作用。 結(jié)果：用經(jīng)過(guò)LPS刺激過(guò)24h的巨噬細(xì)胞的上清液作用于星狀細(xì)胞相比直接加入LPS刺激24h星狀細(xì)胞的組,纖維化相關(guān)的各項(xiàng)指標(biāo)α-SMA、collagen-I、IL-1β IL-18、IL-6以及P2X7r等的mRNA表達(dá)提高；經(jīng)過(guò)LPS刺激過(guò)4h的星狀細(xì)胞中,ATP相關(guān)的P2X7r也可以促進(jìn)上述指標(biāo)的表達(dá),該受體的抑制劑A438079可以降低細(xì)胞因子的表達(dá)水平；在對(duì)于IL-1p的蛋白分析結(jié)果可以看出P2X7受體的激活可以催化IL-1β前體的成熟。 結(jié)論：實(shí)驗(yàn)證明,巨噬細(xì)胞在一定程度上可以促進(jìn)肝星狀細(xì)胞的激活；ATP相關(guān)的P2X7r對(duì)于星狀細(xì)胞激活,對(duì)炎癥反應(yīng)的發(fā)生均起到促進(jìn)作用。其研究可以在未來(lái)通過(guò)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(xué)位授予單位】：延邊大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R575

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本文編號(hào)：1559960