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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 small peptides containing RGD (Arg-Gly-Asp) on platelet aggregation inhibition, thrombus weight and vascular structure by binding to platelet integrin αⅡbβ (3GPⅡb / Ⅲ) a. Methods Whole blood of 10 healthy volunteers without cardiovascular and cerebrovascular diseases was collected and platelet-rich plasma (PRP) was separated. Platelet-rich plasma (6.25,12.5,25,50,100, 200μmol / L) RWR on ADPNa2 induced platelet aggregation inhibition rate; respectively 0.3,0.6,1.2mg / kgRWR rabbit and 0.6,1.2,2.4 mg / kg RWR role in rats , Established rabbit arterial venous bypass thrombosis model and rat ferric chloride thrombosis model, observed changes in thrombus weight and vascular tissue structure changes. Results With the increase of RWR dose, the maximum platelet aggregation rate and platelet aggregation inhibition rate increased. The IC50 of RWR on platelet aggregation inhibition rate was 16.0 μmol / L. With the increase of RWR dosage, the weight of thrombus decreased, the inhibition rate of thrombosis increased, the extent of occlusion of blood vessel weakened and the intravascular cavity increased. Conclusion The small peptide of RWR inhibits the platelet aggregation and antithrombosis by binding with the receptor of platelet integrin αⅡbβ (3GPⅡb / Ⅲ).