洛伐他汀保护内皮祖细胞的机制研究

目的探讨洛伐他汀(lovastatin)保护内皮祖细胞(en-dothelial progenitor cells,EPCs)的机制。方法EPCs与洛伐他汀或者血凝素样氧化型低密度脂蛋白受体(lectin-like oxi-dized low density lipoprotein receptor,LOX-1)的特异性阻断抗体(LOX-1 mAb)预处理24 h后,再与氧化型低密度脂蛋白(oxidized low density lipoprotein,oxLDL)孵育48 h。然后,检测EPCs迁移、粘附和管状结构形成能力。为探讨洛伐他汀的作用机制,检测EPCs生成一氧化氮(nitric oxide,NO)的量,内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)和LOX-1蛋白及mRNA表达。结果oxLDL抑制EPCs迁移、粘附及管状结构形成能力,降低NO产生、eNOS蛋白及mRNA表达,增加LOX-1蛋白及mRNA表达。洛伐他汀和LOX-1 mAb恢复EPCs功能,逆转oxLDL对NO、eNOS及LOX-1的调节。结论洛伐他汀通过调节eNOS和LOX-1而保护EPCs免受oxLDL的损害。

The mechanisms of lovastatin protecting endothelial progenitor cells

Aim To explore the mechanisms of lovastatin protecting EPCs.Methods EPCs were preincubated with lovastatin or LOX-1 mAb for 24 h and then exposed to oxLDL for 48 h.The abilities of migration,adhesion,and tube structure formation of EPCs were examined.To explore the mechanisms,the level of NO,the expression of eNOS and LOX-1 protein and mRNA were assayed.Results Incubation of EPCs with oxLDL resulted in the impairment of migration,adhesion and tube structure formation.Furthermore,oxLDL caused the decrease of NO generation,the down-regulation of eNOS mRNA and protein expression,the up-regulation of LOX-1 mRNA and protein expression.However,the detrimental effects of oxLDL on EPCs function were attenuated by lovastatin and LOX-1 mAb.Moreover,the effects of oxLDL on NO generation,eNOS and LOX-1 expression were reversed by lovastatin and LOX-1 mAb.Conclusion Lovastatin protects EPCs by the regulation of eNOS and LOX-1 expression.