精-甘-天冬-丝氨酸肽抑制血小板活化的胞内信号转导机制  

The Mechanism of Intracellular Signal Transduction of Arg-Gly-Asp-Ser(RGDS)Peptide Inhibiting Rat Platelet Activation

作　　者：姚兴海[1,2] 庞永政[1,2] 马治中 苏静怡[1,2] 唐朝枢[1,2] 

机构地区：[1]北京医科大学心血管基础研究所 [2]中西医结合教研室

出　　处：《基础医学与临床》1999年第1期65-68,共4页Basic and Clinical Medicine

摘　　要：本工作在凝血酶活化的大鼠血小板上，观察ＲＧＤＳ肽对血小板聚集，蛋白磷酸化及丝裂素活化蛋白激酶（ＭＡＰＫ）活性的影响，结果发现，ＩＵ／ｍＬ凝血酶明显引起血小板聚集，９５和６６ｋＤ蛋白磷酸化及ＭＡＰＫ活性的增加，应用５０、１００、２００μｍｏｌ／ＬＲＧＤＳ肽共向孵育，呈浓度依赖地抑制凝血酶引起的血小板聚集和ＭＡＰＫ活性，且两者呈正相关（ｒ＝０．８１，Ｐ＜０．０１）。ＲＧＤＳ肽亦呈浓度依赖地抑制凝血酶诱导的９５和６６ＫＤ蛋白磷酸化，与其抑制ＭＡＰＫ活性呈明显正相关（ｒ＝０．４１，Ｐ＜０．０５和ｄ．５３，Ｐ＜０．０１）。提示，ＭＡＰＫ系统参与了凝血酶引起的Ｗ小板聚集，ＲＧＤＳ肽抑制血小板聚集机理之一可能是通过干预血小板内信号传导途径所致。The aim of this work is to investigate the effect of Arg-Gly-Asp-Ser (RGDS) peptide on platelet aggregation and Mitogen-activated protein kinase (MAPK) activity . Experiments were performed on thrombin activated rat platelets in vivo . Results shotwed that thrombin , when incubated with platelets , obviously induced platelet aggregation and enhanced MAPK activity. When platelets and thrombin were incubated together with 50, 100, 200μmol/L RGDS peptide it was found that RGDS markedly inhibit platelet aggregation and MAPK activation in a concentration-dependent manner and the degree of inhibition of the latter two parameters are in positive relationship (r=0.81 , P.0.0 1 ) . RGDS pep- tide also obviously inhibit 95 and 66kD protein phosphorylation in concentration-dependent manner and the degree of inhibition between protein phosphorylation and MAPK activation are in positive relationship . The results suggested that MAPK might be involved in the underlining mechanism of thrombin induced platelet aggregation; the inhibitory action of RGDS peptide on platelet aggregation was realized through its influence on intracellular signal transduction in thrombin activation of platelets .

关 键 词：RGDS肽 血小板聚集 蛋白磷酸化 信号传导 MAPK 

分 类 号：R973[医药卫生—药品]