Objectives: To investigate the thrombolysis with recombinant human prourokinase (rhPro-UK) on thromboembolic stroke in rats at different therapeutic time windows (TTW). Methods: Rats were subjected to embolic middle cerebral artery occlusion. RhPro-UK and positive control drugs rt-PA,UK were administered 3 h, 4.5 h, 6 h after inducing thromboem-bolic stroke. Neurological deficit scoring (NDS) was evaluated at 6 h and 24 h after the treatment. The lesion volume in cerebral hemispheres was measured by MRI scanning machine after 6 h of thrombolysis, and the infarct volume was measured by TTC stain, together with hemorrhagic volume quantified by a spectrophotometric assay after 24 h of thrombolysis. Results: RhPro-UK 10, 20 × 104 U/kg significantly improved the NDS after cerebral thromboembolism in rats at 3 h, 4.5 h TTW, and at the 6 h TTW, the NDS was improved by 28.0% (P = 0.0690) and 29.2% (P = 0.0927) at 6 h and 24 h after rhPro-UK 20 ×104 U/kg administration, respectively. RhPro-UK 10, 20 × 104 U/kg significantly reduced the brain lesions measured by MRI at 3 h and 4.5 h TTW. RhPro-UK 10, 20 × 104 U/kg significantly reduced the cerebral infarction measured by TTC at 3 h, 4.5 h TTW. There was no increase in cerebral hemorrhage compared with untreated group after rhPro-UK administration. Conclusions: RhPro-UK had an obvious therapeutic effect on ischemic stroke caused by thrombosis, and could be started within 4.5 h TTW with less side effects of cerebral hemorrhage than that of UK.

中文翻译：

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大鼠栓塞性中风后3至6小时用rhPro-UK进行溶栓。

目的：研究重组人原尿激酶（rhPro-UK）在不同治疗时间窗（TTW）对大鼠血栓栓塞性卒中的溶栓作用。方法：将大鼠大脑中动脉栓塞。诱导血栓栓塞性中风后3 h，4.5 h，6 h给予RhPro-UK和阳性对照药物rt-PA，UK。治疗后6小时和24小时评估神经功能缺损评分（NDS）。溶栓后6 h，用MRI扫描仪测量脑半球病变体积，溶栓后24 h，用TTC染色法测定梗死体积，并通过分光光度法定量测定出血量。结果：RhPro-UK 10、20×104 U / kg显着改善了脑血栓栓塞后3 h，4.5 h TTW和6 h TTW大鼠的NDS，在施用rhPro-UK 20×104 U / kg后6小时和24小时，NDS分别改善了28.0％（P = 0.0690）和29.2％（P = 0.0927）。RhTW-UK 10、20×104 U / kg可显着减少TTW在3 h和4.5 h时通过MRI测量的脑部病变。RhTW-UK 10、20×104 U / kg显着降低了TTC在3、4.5 h TTW时测得的脑梗塞。rhPro-UK给药后与未治疗组相比，脑出血没有增加。结论：RhPro-UK对由血栓形成引起的缺血性中风具有明显的治疗作用，可在TTW后4.5小时内开始治疗，与英国相比，脑出血的副作用更少。20×104 U / kg可显着减少TTW在3 h和4.5 h时通过MRI测量的脑部病变。RhTW-UK 10、20×104 U / kg显着减少了TTC在3 h，4.5 h TTW测得的脑梗塞。rhPro-UK给药后与未治疗组相比，脑出血没有增加。结论：RhPro-UK对由血栓形成引起的缺血性中风具有明显的治疗作用，可在TTW后4.5小时内开始治疗，与英国相比，脑出血的副作用更少。20×104 U / kg可显着减少TTW在3 h和4.5 h时通过MRI测量的脑部病变。RhTW-UK 10、20×104 U / kg显着降低了TTC在3、4.5 h TTW时测得的脑梗塞。rhPro-UK给药后与未治疗组相比，脑出血没有增加。结论：RhPro-UK对由血栓形成引起的缺血性中风具有明显的治疗作用，可在TTW后4.5小时内开始治疗，与英国相比，脑出血的副作用更少。