洛伐他汀保护内皮祖细胞的机制研究

The mechanisms of lovastatin protecting endothelial progenitor cells

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。

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.