瑞舒伐他汀抑制C反应蛋白诱导的血管内皮细胞血小板反应蛋白1 mRNA表达  

Rosuvastatin Inhibited the Expression of Thrombospondin-1 mRNA Induced by C-Reactive Protein in Vascualr Endothelial Cells

作　　者：王海蓉[1] 朱刚艳[2] 陈德良[1] 张琳[1] 巢升平[1] 干学东[1] 熊世熙[1] 

机构地区：[1]武汉大学中南医院心内科 [2]武汉大学人民医院老年病科,湖北省武汉市430071

出　　处：《中国动脉硬化杂志》2010年第8期599-602,共4页Chinese Journal of Arteriosclerosis

基　　金：湖北省自然科学基金(2009CDB059);中国科学院淡水生态与生物技术国家重点实验室开放基金(2010FB12)资助

摘　　要：目的研究瑞舒伐他汀对C反应蛋白诱导的人血管内皮细胞血小板反应蛋白1表达的影响。方法体外培养人血管内皮细胞,ELISA和RT-PCR检测C反应蛋白对血管内皮细胞血小板反应蛋白1表达的剂量与时间效应。Western blotting检测信号蛋白p38MAPK的表达水平。结果 C反应蛋白以剂量和时间依赖方式显著增加血管内皮细胞血小板反应蛋白1 mRNA表达,p38MAPK表达增加,其抑制剂SB203580减少p38MAPK的磷酸化及血小板反应蛋白1 mRNA表达水平,瑞舒伐他汀显著抑制p38MAPK表达及血小板反应蛋白1 mRNA和蛋白的表达。结论 C反应蛋白至少通过p38MAPK磷酸化途径直接诱导血管内皮细胞血小板反应蛋白1表达,促进细胞炎症反应,而瑞舒伐他汀抑制C反应蛋白的这种效应。Aim Although C-reactive protein（CRP） is widely used as an inflammatory marker of cardiovascular disease,statins showed a variety of additional effects that may contribute to their protective vascular benefit.However,it is not fully understood whether CRP exerts direct proinflammatory effects on human vascular endothelial cells（HUVEC）. Methods Thrombospondin-1（TSP-1） plays a critical role in the development of atherosclerosis and thrombous.Vascualr endothelial cells were incubated with purified CRP at clinically relevant concentrations（5,10,20 and 40 mg/L）.The protein and transcript levels of the TSP-1 were determined by ELISA and RT-PCR respectively.Also,the phosphorylation of p38MAPK was studied via Western blotting analysis. Results In HUVEC,purified CRP significantly induced the protein release and mRNA expression of TSP-1 in a dose-and time-dependent manner respectively.SB203580（a specific p38MAPK inhibitor） efficiently suppressed these effects of CRP as well as rosuvastatin（10 μmol/L）.CRP triggered the phosphorylation of p38MAPK signal transduction. Conclusion CRP induces TSP-1 protein release and mRNA expression from vascular endothelial cells via activation of the p38MAPK signaling pathways,suggesting that CRP plays an important role in the propagation and prolongation of inflammation in vascular inflammation.

关 键 词：C反应蛋白 血小板反应蛋白1 血管内皮细胞 P38MAPK 

分 类 号：R363[医药卫生—病理学]