重组葡激酶动静脉溶栓治疗犬急性脑梗死的研究

目的探讨重组葡激酶（r—Sak）溶栓的安全性、有效性以及溶栓的时间窗。方法成年比格犬24条，数字表法随机等分为对照组、r—Sak 6h动脉溶栓组和3h静脉溶栓组。用介入技术建立犬急性脑梗死模型，溶栓前行脑血管造影，分别经动脉和静脉进行治疗（对照组和6h动脉溶栓组：分别在栓塞后6h经颈内动脉注入生理盐水10ml和r—Sak0．2mg／kg＋生理盐水10ml；3h静脉溶栓组：栓塞后3h经静脉注入r—Sak0．2mg／kg＋生理盐水10m1），在溶栓后30、60及120min分别行脑血管造影复查，并在溶栓前30min，溶栓后30、60及120min抽取犬静脉血检测血浆凝血酶原时间（PT）、活化的部分凝血活酶时间（APTT）和D-二聚体。栓塞后24h处死动物行病理检查。结果溶栓后6h动脉溶栓组、3h静脉溶栓组和对照组有效的血管数分别为11支（11／13）、8支（8／11）和1支（1／10），差异有统计学意义（P〈0．01）；其中完全通畅的血管分别是6支（6／13）、2支（2／11）和0支（0／10），差异有统计学意义（P〈0．05），但6h动脉溶栓组和3h静脉溶栓组间有效和完全再通的血管数比较差异均无统计学意义（P=0．630和0．211）。溶栓后PT、APTT在r-Sak溶栓组均显著延长，各组的D-二聚体在溶栓前后无明显变化（P值均〉0．05）。24h后动物均存活，6h动脉和3h静脉溶栓组临床症状较轻，病理检查未发现脑出血并发症。结论r-Sak动脉内6h溶栓治疗安全有效，早期血管再通效果较好。

Experimental study of intra-arterial and intravenous recombinant staphylokinase in canine model with acute ischemic stroke

Objective To discuss the safety,efficacy and time window of thombolysis using recombinant staphylokinase(r-Sak).Methods The model of acute cerebral infarction was established with interventional embolization technique in 24 adult beagle dogs,which were randomly divided into 3 groups including control group,6 h intra-arterial group and 3 h intravenous group.Angiography was performed before thrombolysis.We administered r-Sak for thrombolysis(10 ml of saline in control group,0.2 mg/kg of r-Sak in the intra-arterial group through left internal carotid artery 6 h after embolization,and 0.2 mg/kg of r-Sak in the intravenous group through femoral vein 3 h after embolization).Follow-up angiography was repeated half,1 and 2 hours after thrombolysis.The plasma levels of PT,APTT and D-dimer were assayed at the time points of 30 min before thrombolysis,30 min,60 min and 120 min after thrombolysis.These canines were sacrificed,and their brains were taken out for pathological study at 24 hours after embolization.Results The recanaled vessels at 2 hours after thrombolysis was 11(11/13) in the intra-arterial group,8(8/11) in r-Sak intravenous group and 1(1/10) in control group,and the vessels of complete recanalization was 6(6/13),2(2/11) and 0(0/10),respectively.There were statistically significant differences among the three groups (P=0.001 and P=0.035 respectively),but there were no statistically significant differences between the intra-arterial and the intravenous groups (P=0.630 and P=0.211).The PT and APTT are significantly prolonged in the thrombolytic groups.The levels of D-dimer was not changed after thrombolysis (P＞0.05). All dogs were alive 24 h ours after embolization.The clinical presentations in the thrombolytic groups were better.Pathologically,there were no cerebral hemorrhage in all groups.Conclusion r-Sak has strong effect of thrombolysis,and its complication of intracerebral hemorrhage is rare.The intra-arterial thrombolysis 6 h after embolization using r-Sak is safe and effective.