四肽KRDS对犬血小板功能及动脉血栓形成的抑制作用

INHIBITION EFFECTS OF KRDS ON PLATELET FUNCT ION AND ARTERIAL THROMBUS FORMATION IN DOGS

来自人乳转铁蛋白的四肽(赖—精—门冬—丝氨酸,K RDS)能抑制ADP诱导的犬血小板聚集反应(IC_(50):350μmol/L)和花生四烯酸诱导的血栓烷B_2的产生(IC_(50):175μmol/L),同时,KRDS能抑制凝血酶诱导的血小板表面α—颗粒膜蛋白(GMP-140)的表达(IC_(50):350μmol/L及5—羟色胺的释放(IC_(50):525μmol/L)。另外,KRDS能抑制犬股动脉实验血栓的形成,制备血栓模型4h后,离体血栓的重量为对照组的50%,以^(125)Ⅰ—SZ-51(抗GMP-140的单抗)为示踪剂,离体血栓与血液的放射活性比值仅为对照组的16%。结果提示:四肽KRDS不仅能抑制犬血小板的聚集和释放功能,对体内血栓的形成也有明显的抑制作用,为一生理性抗血栓寡肽。

KRDS(Lys-Arg-Asp-Ser), a tetrapeptide from human lactotrans-ferrin, inhibited ADP-induced platelet aggregation ( IC50 350μmol/L ) and arachidonic acid induced thromboxane B2 generation (IC50 175 μmol/L) . In addition, thrombin-induced serotonin release was in-hibited by KRDS(IC50 525μmol/L ) and the expression of alpha-granule membrane protein (GMP-140) on the platelet surface was also inhibited ( IC50 350μmol/L ) · In experimental arterial thrombosis in dogs, KRDS ( 5μmol/kg) and 123I-SZ-51 ( a monoclonal antibody against GMP-140) were injected before operation and after the thrombus formation respectively. In KRDS group the weight of removed thrombus reduced to 50% of that in controls. The radioactivity ratio between removed thrombus and blood per mg was only 16% of that in controls. These results indicate that KRDS can inhibit not only the platelet aggregation and secretion, but the thrombus formation as well. Therefore, KRDS is a promising anti- thrombotic tetrapeptide.