血小板血栓形成过程中脂蛋白(a)作用的实验研究

The effects of lipoprotein(a) on platelets thrombosis: experimental studies

目的 研究脂蛋白 (a) [Lp(a) ]对血小板血栓形成的作用及其机理。方法 制备健康成人血小板 ,设分别加Lp(a)及凝血酶的两个实验组及空白对照组 ,观察三组血小板膜、浆蛋白激酶C(M PKC ,P PKC)活性变化及加Lp(a)组与空白对照组 ,血小板蛋白激酶C(PKC)底物分子量为 470 0 0的蛋白磷酸化程度。结果 Lp(a)组随Lp(a)浓度升高及其作用时间延长 ,血小板P PKC活性降低 ,M PKC活性增高 ,与凝血酶组作用相似 ,两组血小板M PKC活性的增高与空白对照组比较差异均有非常显著意义 (P <0 .0 1) ,血小板P PKC的降低Lp(a)组比凝血酶组更明显 ,与空白对照比较 ,差异分别有非常显著 (P <0 .0 1)及显著意义 (P <0 .0 5 ) ;加Lp(a)组随Lp(a)的浓度增高及其作用时间的延长 ,血小板PKC底物蛋白磷酸化程度亦不断增高 ,均明显高于空白对照组。结论 Lp(a)能激活血小板 ,使血小板PKC活性增高 ,PKC底物蛋白磷酸化程度增强 。

Objective To investigate the effect and mechanism of lipoprotein(a)[Lp(a)] on platelet thrombosis. Methods Freshly prepared platelets from healthy donors were incubated with Lp(a) and thrombin respectively. Control incubation was performed with platelet buffer. The activity of protein kinase C(PKC) in membrane and plasma of platelets and the degree of phosphorylation of the 47?000 substrate of PKC in platelets were tested. Results The activity of PKC in plasma decreased while that in membrane increased with the increase of the concentration and prolonged incubation time of Lp(a), very similar to the effect of thrombin.Compared with the control group, we found that the activity of PKC in membrane in both test groups increased very significantly ( P <0.01); the activity of PKC in plasma in Lp(a) group decreased more markedly than that in thrombin group, with a very significant ( P <0.01) or a significant ( P <0.05) difference compared with that in the control group. With the increase of the concentration and prolonged incubation time of Lp(a), the degree of phosphorylation of the 47?000 substrate increased gradually, higher than that in the control group. Conclusions Lp(a) can activate platelet, increase the activity of PKC,and increase the degree of phorphorylation of the 47?000 substrate; Lp(a) directly promotes platelet thombosis.