rt-PA联合亚低温治疗对缺血性脑卒中出血转化的干预研究

目的观察缺血3h时间窗内和超过时间窗采用重组组织型纤溶酶原激活剂(rt-PA)和rt-PA联合亚低温对脑缺血再灌注后出血转化干预的效果。方法利用线栓法制作SD大鼠大脑中动脉闭塞3h和4h再灌注模型,将大鼠随机分为生理盐水对照组、rt-PA组、rt-PA+亚低温组,并设立伪手术组对照。rt-PA+亚低温组缺血再灌注后给予3h亚低温干预。缺血再灌注24h后处死动物,测定出血量。结果闭塞3h模型大鼠中,rt-PA组与生理盐水对照组、rt-PA组与rt-PA+亚低温组比较,出血量增加(P<0.05);闭塞4h模型大鼠中,rt-PA组与生理盐水组、rt-PA组与rt-PA+亚低温组比较,出血量增加(P<0.05);闭塞4hrt-PA组大鼠与闭塞3hrt-PA组大鼠比较,出血量增加(P<0.05)。结论rt-PA可以使血管再通后的出血转化量增加;时间窗外使用rt-PA较时间窗内使用rt-PA出血转化量增加;溶栓时联合亚低温治疗可减轻rt-PA出血转化的副作用,延长溶栓治疗时间窗。

Effects of rt-PA Combined with Mild Hypothermia on Hemorrhagic Transformation after Ischemic Stroke in Rats

Objective To investigate the effects of recombinant tissue-type plasminogen activator (rt-PA) combined with mild hypothermia on the hemorrhagic transformation after cerebral ischemia-reperfusion within or out of the therapeutic time window in rats.Methods The focal cerebral ischemia-reperfusion 3 and 4 hours models of rats were established by middle cerebral artery occlusion (MCAO) 3 or 4 hours. The rats were randomly divided into the normal saline group (group NS), normothermia rt-PA group (group rt-PA), rt-PA combined with hypothermia group (group rt-PA +HT), and sham-operation group. Brain mild hypothermia was achieved after ischemia reperfusion and maintained 3 hours. Rats were sacrificed 24 h after ischemia reperfusion, and the amount of bleeding was measured.Results The amount of bleeding significantly reduced in the group rt-PA+HT compared with group rt-PA, which obviously increased in the group rt-PA compared with group NS ( P<0.05); there was a significant difference between rt-PA groups MCAO 3 hours and 4 hours ( P<0.05).Conclusion rt-PA can increase hemorrhagic transformation volume; hemorrhagic transformation volume is higher if treated by rt-PA within 3 h therapeutic time window than treated beyond the time window; mild hypothermia should possibly prevent the development of hemorrhagic transformation and prolong the therapeutic time window of thrombolytic intervention in ischemic stroke.