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阿托伐他汀增加单核细胞过氧化物酶增殖体激活受体γ表达改善炎症反应
Modulation of inflammatory response and peroxisome proliferator-activated receptor gamma expression by atorvastatin in human peripheral blood monocytes
【摘要】 目的 研究阿托伐他汀对人外周血单核细胞过氧化物酶增殖体激活受体γ(PPARγ)及其单核细胞趋化蛋白 1(MCP 1)和金属蛋白酶 9(MMP 9)的影响。方法 分离健康人外周血单核细胞并加入不同浓度的阿托伐他汀 (0 1~ 10 μmol/L)共同培养 2 4h ,采用RT PCR检测PPARγ和MCP 1的表达。并采用定量夹心酶免疫吸附测定法检测单核细胞培养上清液中MMP 9和MCP 1的浓度。结果 阿托伐他汀能明显增加人外周血单核细胞PPARγ的表达 ,1、10 μmol/L阿托伐他汀使PPARγ的表达明显增加 (P <0 0 5 ) ,并能明显抑制人外周血单核细胞MCP 1的表达和分泌。与基础状态相比 ,阿托伐他汀降低单核细胞培养上清MCP 1和MMP 9浓度分别达 73%和 6 2 % (P <0 0 5 ) ,呈浓度依赖性。结论 阿托伐他汀能够抑制人外周血单核细胞MCP 1的表达和分泌以及MMP 9的分泌 ,说明它具有抗炎作用 ,其抗炎作用可能与其改善PPARγ表达有关。
【Abstract】 Objective To study the effect of atorvastatin on the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and monocyte chemoattractant protein-1 (MCP-1 ) and the secretion of MCP-1 and matrix metalloproteinase-9 ( MMP-9) in human peripheral blood monocytes. Methods Peripheral blood monocytes of healthy human were isolated and incubated with different concentration of atorvastatin (0.1~10 μmol/L) for up to 24 hours. PPARγ and MCP-1 expression in monocytes was analyzed by reverse transcription polymerase chain reaction (RT-PCR). MCP-1 and MMP-9 levels in monocytes culture supernatants were measured by enzyme-linked immunosorbent assays (ELISA). Results Atorvastatin increased expression of PPARγ in human monocytes. Atovastatin of 1 and 10 μmol/L increased expression of PPARγ. Atorvastatin inhibited significantly the expression of MCP-1. Compared with basiline, atorvastatin reduced productions of MCP-1 and MMP-9 secreted by human peripheral blood monocytes up to 73% and 62% respectively(P<0.05), which was in a dose-dependent manner. Conclusion These findings suggest that atorvastatin has anti-inflammatory effects which are probably related to its activating effect of PPARγ.
【Key words】 Antilipemic agents; Peroxisome proliferator-activated receptor-gamma; Inflammation;
- 【文献出处】 中华心血管病杂志 ,Chinese Journal of Cardiology , 编辑部邮箱 ,2004年04期
- 【分类号】R543
- 【被引频次】56
- 【下载频次】228