洛伐他汀对THP-1细胞分化成泡沫细胞过程中清道夫受体A表达及MCP-1、TNF-α水平的影响

摘要

目的 观察洛伐他汀对THP-1细胞株分化成泡沫细胞过程中清道夫受体A(SRA)表达及MCP-1和TNF-α的水平的影响.方法 培养THP-1细胞,佛波脂(PAM)使之巨噬化,氧化型低密度脂蛋白使巨噬细胞形成泡沫细胞,将其分为巨噬细胞组(对照组)、泡沫细胞组、泡沫细胞+洛伐他汀组,各组细胞孵育24 h,用ELISA法检测各组细胞培养液中MCP-1、TNF-α水平.将SRA特异性配体DiI-Ac-LDL与细胞孵育6 h,用荧光显微镜观察各组细胞SRA的表达.结果 THP-1细胞经佛波脂和氧化型低密度脂蛋白孵育后,有大量泡沫细胞形成.与对照组相比,泡沫细胞组,SRA蛋白活性及MCP-1、TNF-α水平明显升高(P＜0.05),洛伐他汀干预后,其水平较泡沫细胞组显著降低(P＜0.05).结论 SRA、MCP-1及TNF-α在THP-1细胞分化成泡沫细胞过程中发挥着重要作用;洛伐他汀可抑制SRA、MCP-1及TNF-α的表达,这可能为其抗动脉粥样硬化的机制之一.%Objective To study the effect of lovastatin on expressions of scavenger receptor A (SRA), MCP-1 and TNF-α. Methods THP-1 cells were cultured. Macrophages were induced from THP-1 cell by PMA. Models of foam cells were built by incubating macrophages with 50 mg/L ox-LDL. Cells were divided into macrophages, foams and foams plus lovastatin groups. Cells were incubated for 24 h,MCP-1 and TNF-α in cell substratum were measured by ELISA. SRA expression was observed under fluorescent microscope after incubated with DiI-Ac-LDL for 6 h. Results Macrophages incubated with ox-LDL formed into foam cells successfully. Compared to the control cells,the activity of protein SRA, MCP-1 and TNF-α concentration in ox-LDL treated cells were increased( all P ＜0. 05 ). But lovastatin significantly attenuated these changes( P ＜ 0. 05 ). Conclusions SRA, MCP-1 and TNF-αexpressions play a key role in the course of THP-1 differentiated into foam cells and lovastatin can inhibit the expression of SBA, MCP-1 and TNF-α, which is one of mechanisms of lovastatin's anti-arteriosclerosis effect.