瑞舒伐他汀对内皮细胞中组织因子途径抑制物表达的影响  

Effects of rosuvastatin on the expression of tissue factor pathway inhibitor in vascular endothelial cells

作　　者：侯英健[1] 韩艳梅[1] 史小琴[1] 李大海[2] 田媛[2] 

机构地区：[1]河北大学基础医学院 [2]河北大学附属医院,河北保定071000

出　　处：《中国药理学通报》2012年第8期1146-1149,共4页Chinese Pharmacological Bulletin

基　　金：保定市科技攻关项目(No 11ZF087)

摘　　要：目的探讨瑞舒伐他汀对组织因子途径抑制物(TF-PI)表达的调节作用及机制。方法培养人脐静脉内皮细胞(HUVECs),给予多种剂量的瑞舒伐他汀和(或)肿瘤坏死因子-α(TNF-α)、磷酸腺苷激活的蛋白激酶(AMPK)抑制剂与激活剂处理细胞,利用实时定量PCR、Western blot技术检测内皮细胞中TFPI表达的变化。结果 TNF-α下调内皮细胞中TFPI的的表达水平,而这一作用被瑞舒伐他汀所阻断。而且,瑞舒伐他汀呈时间及剂量依赖性上调TFPI的mRNA与蛋白水平。AMPK抑制剂———Compoud C则可逆转瑞舒伐他汀对TFPI表达的上调作用,而AMPK激动剂———Aicar则具有与瑞舒伐他汀相似的上调TFPI的作用。结论瑞舒伐他汀通过激活AMPK途径上调血管内皮细胞中TFPI的表达。Aim To explore the underlying mechanism and effects of rosuvastatin on the expression of tissue factor pathway inhibitor （TFPI） in human umbilical vein endothelial cells （HUVECs）. Methods HUVECs were isolated and primarily cultured in vitro. After the treatment of rosuvastatin and tumor necrosis factor α（TNF-α）, TFPI expression was determined in HUVECs with real-time PCR and Western blot. Results This study showed that TNF-α challenge down-regulated TFPI expression in HUVECs, but its suppressive effect was reversed partially by rosuvastatin, a lipidlowering drug. Furthermore, rosuvastatin was found to modify TFPI expression at mRNA and protein levels in time and dose-dependent manners. Aicar, an agonist of AMP-activated protein kinase （AMPK） exerted a similar effect on statin, whereas Compoud C, an inhibitor of AMPK, was demonstrated to block the rosuvastatin-enhanced TFPI expression. Conclusion Through activation of AMPK pathway, rosuvastatin potentiates TFPI expression serving anti-inflammatory and anti- thrombotic functions in endothelial cells.

关 键 词：瑞舒伐他汀 组织因子途径抑制物 人脐静脉血管内皮细胞 磷酸腺苷激活的蛋白激酶 血栓 羟甲基戊二酰辅酶A还原酶抑制剂 

分 类 号：R322.12[医药卫生—人体解剖和组织胚胎学] R329.24[医药卫生—基础医学]