动脉粥样硬化模式家兔血小板对一氧化氮反应性的研究

目的 :研究在动脉粥样硬化的发展过程中内皮脱功能是否导致血小板对一氧化氮的反应性降低。方法 :家兔用含 1%胆固醇的饲料喂养 12周建立动脉粥样硬化模型。在给予高胆固醇饮食的过程中每 4周测定血清NOx水平以及血小板对NO供体SNP的反应性。 12周后测定血脂水平、观察主动脉的形态学变化和内皮依赖性舒张反应。结果 :高胆固醇饮食显著增高血清胆固醇和LDL水平 ,血小板聚集性增强 ,电镜扫描显示主动脉内皮细胞严重受损 ,乙酰胆碱诱导的内皮依赖性舒张反应明显降低。虽然高胆固醇饮食家兔在动脉粥样硬化过程中血清NOx水平与正常饮食家兔没有显著差异 ,但NO供体SNP对ADP 诱导的血小板聚集的抑制率显著低于正常饮食组。结论 :高胆固醇和LDL血症导致的内皮脱功能降低了血小板对NO的反应性。

A Decreased Responsiveness of Platelet to Nitric Oxide in Cholesterol-Fed Rabbits

Objective:To determine whether endothelial dysfunction leads to an abnormal responsiveness of platelet to nitric oxide(NO)during the development of atherosclerosis. Methods:Rabbits were fed a 1% cholesterol chow for 12 weeks to induce atherosclerosis.Serum NOx levels and the responsiveness of platelet to NO donor SNP were determined every 4 weeks during maintaining on a chow containing 1% cholesterol.The measurement of serum lipids and the examination of morphological feature and endothelial-dependent relaxation of aorta were performed after 12 weeks of cholesterol diet. Results:Cholesterol diet significantly increased serum levels of cholesterol and LDL,caused a remarkable platelet hyperaggregability,and produced an evident endothelial dysfunction as indicated by the diminished vasorelaxation induced by acetylcholine and endothelial cell lesion as exhibited by scanning electron microscope examination.The percentage of inhibition of ADP-induced platelet aggregation by NO donor SNP was significantly smaller in cholesterol chow group than that in normal chow group although no significant difference in serum NOx levels between normal and cholesterol chow group was observed throughout the development of atherosclerosis. Conclusion:The present study suggests that the endothelial dysfunction caused by enhanced serum cholesterol and LDL levels induces a decreased responsiveness of platelet to NO.