摘要
目的探讨含RGD(Arg-Gly-Asp)序列的RWR小肽通过与血小板表面整合素αⅡbβ(3GPⅡb/Ⅲ)a结合,对血小板聚集抑制率、血栓重量、血管组织结构的影响。方法取10名无心脑血管疾病的健康志愿者的全血,分离富含血小板的血浆(platelet-rich plasma,PRP),采用血小板聚集仪检测不同剂量(6.25、12.5、25、50、100、200μmol/L)RWR对二磷酸腺苷二钠(ADPNa2)诱导的血小板聚集抑制率的影响;分别用0.3、0.6、1.2mg/kgRWR作用家兔及0.6、1.2、2.4 mg/kg RWR作用大鼠,建立兔动静脉旁路循环血栓模型和大鼠三氯化铁血栓模型,观察血栓重量的变化和血管组织结构的变化。结果随着RWR剂量增加,血小板最大聚集率降低,血小板聚集抑制率增加,RWR对血小板聚集抑制率的半数有效抑制浓度(IC50)为16.0μmol/L。随着RWR剂量的增加,血栓重量减少,血栓形成的抑制率增加,血管腔堵塞程度减弱,血管腔内孔隙增加。结论 RWR小肽通过与血小板表面整合素αⅡbβ(3GPⅡb/Ⅲ)a受体结合,抑制血小板聚集和抗血栓。
Objective To investigate the effect of RWP peptide containing RGD（Arg-Gly-Asp） sequence,combined with integrin α Ⅱb β 3（GPⅡ b / Ⅲ a）receptor on the surface of platelet,on the inhibitory rate of platelet aggregation,thrombus formation and vascular tissue structure.Methods Blood samples of ten healthy volunteers without cardiovascular and cerebrovascular diseases were collected,from which platelet-rich plasma（PRP）was separated.The effect of RWR at various concentrations（6.25,12.5,25,50,100 and 200 μmol / L）on the inhibitory rate of platelet aggregation induced by ADPNa 2 was determined by platelet aggregation analyzer.Rabbits were treated with RWR at concentrations of 0.3,0.6 and 1.2 mg / kg to establish a model of thrombosis with arteriovenous bypass loop,while rats with RWR at concentrations of 0.6,1.2 and 2.4 mg / kg to establish a model of ferric chloride thrombosis,of which the changes of thrombus weight and vascular tissue structure were observed.Results With the increasing RWR concentration,the maximum platelet aggregation rate increased,while the inhibitory rate of platelet aggregation increased,the thrombus weight decreased,the inhibitory rate of thrombus formation increased,the degree of vascular stenosis decreased,and the vascular lumen pore was enlarged.The IC 50 of RWR to inhibitory rate of platelet aggregation was 16.0 μmol / L.Conclusion RWR inhibited platelet aggregation and play an antithrombotic role through binding to integrin α Ⅱb β 3 receptor on the surface of platelet.
出处
《中国生物制品学杂志》
CAS
CSCD
2013年第8期1126-1129,1133,共5页
Chinese Journal of Biologicals
基金
山西省自然科学基金(2012011041-5)
国家自然科学基金青年基金(81101895)
山西省青年科学基金(2010021035-1)
山西省高等学校优秀青年学术带头人支持计划[晋教科(2012)10号]
"重大新药创制"科技重大专项(2012ZX09103301010)
细胞生理学省部共建教育部重点实验室主任基金(2010-11)资助项目
