辛伐他汀对糖基化终产物损伤血小板功能的抑制作用

Effect of simvastatin on the function of platelet damaged by advanced glycation end products

【目的】探讨辛伐他汀抑制糖基化终产物损伤血小板功能的机制。【方法】首先提取正常人血小板作为研究对象并随机分为4组进行对比研究:对照组、辛伐他汀(50μmol/L)组、糖基化终产物(advanced glycation ends products,AGEs)(200 mg/L)组以及辛伐他汀(50μmol/L)和AGEs(200 mg/L)共同作用组。在实验中分别检测3个重要指标,包括血小板功能、一氧化氮(NO)的浓度和cGMP的含量,并应用western blotting检测一氧化氮合酶(endothelial nitric oxide synthase,eNOS)磷酸化水平及其蛋白表达。【结果】辛伐他汀不仅能有效的抑制AGEs对血小板的活化作用,也具有抑制AGEs降低NO释放和cGMP含量的功能。western blotting的结果显示辛伐他汀还具有抑制AGEs降低eNOS磷酸化水平的作用。【结论】辛伐他汀抑制AGEs对血小板的活化作用可能是通过NO/cGMP途径来实现的。

[Objective] To investigate the mechanism of simvastatin to inhibit the function of platelet damaged by advanced glycation end products （AGEs）. [Methods] Normal platelets were employed and sorted into four groups： control group, simvastatin group （50 mmol/L）, AGEs as treatment agent（200 mg/L） group and simvasatatin （50 μmol/L） plus AGEs（200 mg/L） group. Three important factors, including the function of platelets, the concentration of NO and the content of cGMP, were recorded in the experiment. The phosphorylation and protein expression of eNOS were measured with western blotting. [ Results] The experimental results showed that simvastatin not only effectively inhibited the activation of AGEs on platelets, but also displayed high capability of inhibiting AGEs from reducing NO release and cGMP content. The western blotting results indicated that simvastatin inhibited AGEs from reducing eNOS as well. [Conculsion] The inhibiting effect of simvastatin on the activation of AGEs to platelets may be achieved via NO/cGMP route.