延长溶栓时间窗在缺血性脑卒中tPA治疗的临床前研究进展

Preclinical research progress of enlarging thrombolysis time window of ischemic stroke with tissue type plasminogen activator treatment

脑卒中(stroke)是中老年人常见疾病,其具有高发病率、高死亡率和高致残率等特点,已严重威胁人类健康。目前为止,溶栓治疗是缺血性脑卒中最有效的治疗方法,组织型纤溶酶原激活剂(tissue type plasminogen activator,t PA)是唯一被美国FDA批准用于治疗脑卒中的溶栓药物。然而t PA的时间窗只有4.5 h,很少一部分人会在时间窗内接受溶栓治疗,并且当t PA的治疗时间窗超过4.5 h,会显著增加出血性转化(hemorrhagic transformation,HT)的发生率,从而导致脑卒中患者死亡率显著增加。在临床上通常使用联合用药的治疗策略来延长t PA的治疗时间窗,从而减少溶栓带来的不利影响。HT是急性缺血性卒中患者使用组织型纤溶酶原激活剂溶栓治疗后最严重的并发症,极大地限制了t PA的临床应用。本文主要综述了在动物试验中与t PA联合使用能扩大t PA的治疗时间窗并且不增加出血性转化风险的药物,旨在为提高t PA的整体疗效提供研究基础。

Stroke is a common disease in the elderly. The high morbidity,mortality and disability of stroke have threatened human health seriously. So far,thrombolytic therapy is the most effective treatment for cerebral ischemic stroke,and t PA is the only thrombolytic drug for the treatment of stroke which has been approved by the US FDA. However,the time window of t PA is only 4. 5 hours and very few people could receive thrombolysis during this period. Moreover,when the therapeutic time window of t PA is more than 4. 5 hours,the incidence of hemorrhagic transformation will significantly increase,then leads to the rapid increase of the mortality of stroke. Clinically,the method of combination therapy is usually used to prolong the therapeutic window of t PA,which is in order to reduce the adverse effects of thrombolysis. HT is one the most serious complications of patients who take the t PA thrombolytic therapy and it limits the clinical application greatly. This article reviews the therapeutic drugs that can be used in combination therapy to expand the therapeutic time window of t PA and at the same time don＇t increase the probability of hemorrhagic transformation during animal experiment.We aim to provide a research basis for improving the overall effect of t PA.