急性缺血性脑卒中的溶栓药物概况

Thrombolytic drugs for acute ischemic stroke

卒中是导致患者死亡和长期残疾的重要原因之一,在我国其致死率仅次于恶性肿瘤,而87%的卒中患者为缺血性。缺血性脑卒中的发病多与血栓形成有关,溶栓治疗是治疗该病的重要手段之一,目前上市的溶栓药物多为纤维蛋白溶解酶原激活剂,该类药物能直接或间接激活纤维蛋白溶解酶原成纤维蛋白溶解酶,并降解纤维蛋白,从而达到溶栓的目的。从第一代溶栓药链激酶上市至今,共有6种纤维蛋白溶解酶原激活剂上市,其中仅有阿替普酶获FDA批准用于缺血性脑卒中的治疗,其他药物均有临床试验研究结果的支持,在临床也多有应用。但由于该类药物有治疗时间窗狭窄、出血等严重不良反应而限制了更多的患者从中获益,研究者正从药物的特性、剂量、联合用药等方面展开研究,以增强其临床效益。

Stroke is the key cause of long-term disability and the second leading cause of death in China. Of all strokes, 87% are ischemic which is associated with thrombosis. Intravenous thrombolytic therapy for acute ischemic stroke （AIS） is now generally accepted. Thrombolytic agents available today are plasminogen activators with ability of converting plasminogen to the natural fibrinolytic agent plasmin. Plasmin lysis clot by breaking down the fibrinogen and fibrin contained in a clot. Alteplase is the only current lyric agent which US Food and Drug Administration （FDA） approved for AIS. The other five marketed drugs had clinical evidence to treat AIS. Because of their narrow therapeutic time window and risk of systemic bleeding, many patients can not benefit from thrombolytic therapy. Ongoing studies with the aim to promote clinical efficacy by improving drug properties, dosage and combined therapy are in progress.