發(fā)布時(shí)間：2018-09-18 10:12

【摘要】： 目的:本研究旨在探討白介素-6(IL-6)對(duì)THP-1巨噬細(xì)胞源性泡沫細(xì)胞三磷酸腺苷結(jié)合盒轉(zhuǎn)運(yùn)體A1(ABCA1)和三磷酸腺苷結(jié)合盒轉(zhuǎn)運(yùn)體G1(ABCG1)表達(dá)和膽固醇流出的影響,并進(jìn)一步探討其可能機(jī)制。 方法: THP-1單核細(xì)胞經(jīng)佛波酯誘導(dǎo)貼壁后,加入oxLDL誘導(dǎo)其轉(zhuǎn)化為泡沫細(xì)胞,經(jīng)各種因素處理后,用實(shí)時(shí)熒光定量PCR和Western印跡分別檢測(cè)基因和蛋白質(zhì)的表達(dá),運(yùn)用液體閃爍計(jì)數(shù)法檢測(cè)細(xì)胞內(nèi)膽固醇流出,高效液相色譜法分析細(xì)胞內(nèi)總膽固醇、游離膽固醇和膽固醇酯的含量。 結(jié)果:實(shí)驗(yàn)結(jié)果表明,IL-6能夠明顯降低THP-1巨噬細(xì)胞源性泡沫細(xì)胞ABCA1和ABCG1的表達(dá),抑制細(xì)胞內(nèi)膽固醇的流出。IL-6也能夠下調(diào)肝X受體α(LXRα)的表達(dá),抑制LXR特異性激動(dòng)劑T0901317對(duì)ABCA1和ABCG1的表達(dá)。相反, LXRα-siRNA能逆轉(zhuǎn)IL-6下調(diào)ABCA1和ABCG1的作用。同時(shí),IL-6呈劑量和時(shí)間依賴(lài)性誘導(dǎo)JAK1/STAT3的活化,JAK1抑制劑piceastannol能夠抑制IL-6的活化。此外,STAT3小分子干擾RNA和piceastannol能夠逆轉(zhuǎn)IL - 6對(duì)LXRα、ABCA1和ABCG1的抑制作用。 結(jié)論:IL-6能抑制THP-1巨噬細(xì)胞源性泡沫細(xì)胞ABCA1和ABCG1表達(dá)及膽固醇流出。這可能是IL-6通過(guò)活化JAK1-STAT3信號(hào)途徑下調(diào)LXRα水平,從而降低細(xì)胞內(nèi)ABCA1和ABCG1表達(dá)及細(xì)胞內(nèi)膽固醇的流出。
[Abstract]:Aim: to investigate the effects of interleukin-6 (IL-6) on the expression and cholesterol efflux of adenosine triphosphate binding box transporter A1 (ABCA1) and adenosine triphosphate binding box transporter G1 (ABCG1) in THP-1 macrophage derived foam cells. Methods: THP-1 monocytes were induced by phorbol ester and then transformed into foam cells by adding oxLDL. The expression of genes and proteins were detected by real-time fluorescence quantitative PCR and Western blotting. Cholesterol efflux was detected by liquid scintillation counting and the contents of total cholesterol, free cholesterol and cholesterol ester in cells were analyzed by high performance liquid chromatography (HPLC). Results: the results showed that IL-6 could significantly decrease the expression of ABCA1 and ABCG1 in THP-1 macrophage derived foam cells, and inhibit cholesterol efflux. IL-6 could also down-regulate the expression of LXR 偽 in liver. The expression of ABCA1 and ABCG1 was inhibited by LXR specific agonist T0901317. On the contrary, LXR 偽-siRNA reversed the down-regulation of ABCA1 and ABCG1 by IL-6. At the same time, IL-6 induced the activation of JAK1/STAT3 in a dose-and time-dependent manner. JAK1 inhibitor piceastannol could inhibit the activation of IL-6. In addition, the interference of STAT3 with RNA and piceastannol could reverse the inhibitory effect of IL 6 on LXR 偽 -ABCA1 and ABCG1. Conclusion: IL-6 can inhibit the expression of ABCA1 and ABCG1 and cholesterol efflux in THP-1 macrophage derived foam cells. This may be that IL-6 down-regulates the level of LXR 偽 by activating the JAK1-STAT3 signaling pathway, thereby reducing the expression of ABCA1 and ABCG1 and the intracellular cholesterol efflux.
【學(xué)位授予單位】：南華大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2010
【分類(lèi)號(hào)】：R363

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