瑞舒伐他汀抑制C-反应蛋白诱导的晚期内皮祖细胞炎症因子的表达  

Rosuvastatin inhibits up-regulation of inflammatory factors in endothelial outgrowth cells induced by C-reactive protein

作　　者：钟钧琳[1] 彭隆[1] 罗艳婷[1] 刘金来[1] 

机构地区：[1]中山大学附属第三医院心内科,广东广州510630

出　　处：《中国病理生理杂志》2013年第4期597-602,共6页Chinese Journal of Pathophysiology

基　　金：广东省自然科学基金资助项目(No.07001556)

摘　　要：目的:观察瑞舒伐他汀对C-反应蛋白(CRP)诱导晚期内皮祖细胞分泌单核细胞趋化蛋白1(MCP-1)、白细胞介素8(IL-8)、血管细胞黏附分子1(VCAM-1)及细胞间粘附分子-1(ICAM-1)的影响。方法:密度离心法获取人脐血单个核细胞并培养获得晚期内皮祖细胞。以不同浓度和不同时间CRP刺激晚期内皮祖细胞,以及将晚期内皮祖细胞用不同浓度(10-8mol/L、10-7mol/L和10-6mol/L)瑞舒伐他汀预孵育12 h后再用CRP 50 mg/L刺激,观察细胞的炎症变化。采用荧光定量PCR方法检测IL-8、MCP-1、VCAM-1和ICAM-1 mRNA表达情况,用ELISA检测细胞上清液MCP-1和VCAM-1蛋白表达情况。结果:IL-8、MCP-1、VCAM-1和ICAM-1 mRNA表达量及MCP-1和VCAM-1蛋白表达量均随CRP刺激浓度的增高逐渐增加;50 mg/L CRP不同时间刺激下IL-8、VCAM-1和ICAM-1 mRNA表达量在6 h达高峰,MCP-1则在3 h即达高峰,而MCP-1和VCAM-1蛋白水平均随CRP刺激时间增加逐渐增高。而以不同浓度瑞舒伐他汀预孵育,可以浓度依赖性地抑制CRP诱导的晚期内皮祖细胞各炎症因子的表达。结论:不同浓度、不同时间的CRP刺激可增加晚期内皮祖细胞炎症因子表达,进一步证明CRP并非仅仅为炎症标志物;瑞舒伐他汀可显著抑制CRP诱导晚期内皮祖细胞炎症因子的表达,从一个新的角度阐明了瑞舒伐他汀的作用机制。AIM： To study the effects of rosuvastatin on C-reactive protein （CRP）-induced expression of in- flammatory factors in endothelial outgrowth cells （EOCs）. METHODS： Mononuclear cells （MNCs） were isolated from human umbilical cord blood by density gradient eentrifugation. EOCs were treated with CRP at concentration of 5, 10, 25 and 50 mg/L and were exposed to 50 mg/L CRP for different time （0, 3, 6 and 12 h）. In addition, EOCs were pre-incu- bated with rosuvastatin at different concentrations （ 10 -s, 10 -7 and 10 -6mol/L） for 12 h and then stimulated with 50 mg/ L CRP. The mRNA levels of IL-8, MCP-1, VCAM-1 and ICAM-1 in EOCs were measured by quantitative PCR. The pro- tein levels of MCP-1 and VCAM-1 were detected by ELISA. RF^UILTS： CRP dose-dependently increased the mRNA lev- els of inflammatory factors （IL-8, MCP-1, VCAM-1 and ICAM-1 ） and protein levels of MCP-1 and VCAM-1. The mRNA levels of IL-8, VCAM-1, and ICAM-1 in EOCs reached to the peak at 6 h, while MCP-1 peaked at 3 h when treated with 50 mg/L CRP. The protein levels of MCP-1 and VCAM-1 increased in a time-dependent manner. The mRNA and protein levels of the inflammatory factors were significantly decreased by treatment with rosuvastatin at different concentrations. CONCLUSION： CRP is not just an inflammatory marker as CRP induces inflammation in EOCs. Rosuvastatin attenuates CRP-induced inflammatory response in EOCs, indicating a new target for the prevention of atheroscleresis.

关 键 词：炎症 C-反应蛋白 内皮祖细胞 瑞舒伐他汀 

分 类 号：R363[医药卫生—病理学]