【摘要】： 目的:本研究旨在探討白介素-6(IL-6)對THP-1巨噬細胞源性泡沫細胞三磷酸腺苷結合盒轉運體A1(ABCA1)和三磷酸腺苷結合盒轉運體G1(ABCG1)表達和膽固醇流出的影響,并進一步探討其可能機制。 方法: THP-1單核細胞經(jīng)佛波酯誘導貼壁后,加入oxLDL誘導其轉化為泡沫細胞,經(jīng)各種因素處理后,用實時熒光定量PCR和Western印跡分別檢測基因和蛋白質的表達,運用液體閃爍計數(shù)法檢測細胞內(nèi)膽固醇流出,高效液相色譜法分析細胞內(nèi)總膽固醇、游離膽固醇和膽固醇酯的含量。 結果:實驗結果表明,IL-6能夠明顯降低THP-1巨噬細胞源性泡沫細胞ABCA1和ABCG1的表達,抑制細胞內(nèi)膽固醇的流出。IL-6也能夠下調肝X受體α(LXRα)的表達,抑制LXR特異性激動劑T0901317對ABCA1和ABCG1的表達。相反, LXRα-siRNA能逆轉IL-6下調ABCA1和ABCG1的作用。同時,IL-6呈劑量和時間依賴性誘導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IL - 6對LXRα、ABCA1和ABCG1的抑制作用。 結論:IL-6能抑制THP-1巨噬細胞源性泡沫細胞ABCA1和ABCG1表達及膽固醇流出。這可能是IL-6通過活化JAK1-STAT3信號途徑下調LXRα水平,從而降低細胞內(nèi)ABCA1和ABCG1表達及細胞內(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.
【學位授予單位】：南華大學
【學位級別】：碩士
【學位授予年份】：2010
【分類號】：R363

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