膜外二三磷酸核苷水解酶-1(CD39/NTPDase-1)与血栓形成及血管保护研究进展

Progress in nucleoside triphosphate diphosphohydrolase (CD39/NTPDase-1) and thrombotic and vasoprotective effect

血小板保持血管的完整性,当血管受损时参与止血,在病理状态下如冠脉粥样硬化、脑部血管或周围血管受损时血小板活化并聚集,形成血栓造成组织缺血。膜外二三磷酸核苷水解酶-1(NTPDase-1,或称CD39)位于内皮细胞表面,通过水解ADP来减少促血栓物质,抑制血栓形成,保持血管内流动性。此外,水溶性CD39还能明显减弱去甲肾上腺素的释放,表明CD39可通过ATP调节去甲肾上腺素起到心血管保护的作用。在CD39缺失的小鼠脑卒中模型还发现水溶性CD39可改善其后遗症,提示CD39是一种治疗血管血栓及其并发症的新途径。

Blood platelets maintain vascular integrity and promote hemostasis following interruption of vessel continuity.Biochemical or physical damage to coronary,carotid,or peripheral arteries promotes excessive platelet activation and recruitment culminating in vascular occlusion and tissue ischemia.CD39,or NTPDase-1,is an integral component of the endothelial cell surface.It maintains vascular fluidity,acts solely on the platelet releasate,is efficacious in animal models.It metabolically neutralizes a prothrombotic releasate via deletion of ADP—the major recruiting agent responsible for formation of an occlusive thrombus.Meanwhile,solCD39 reduces ischemia-induced norepinephrine release in the heart by modulating adenosine triphosphate（ATP）,which can prevent fatal arrhythmia.Moreover,solCD39 ameliorates the sequelae of stroke in cd39-null mice.CD39 may represent the next generation of cardioprotective and cerebroprotective therapy method.