大鼠急性大脑中动脉闭塞机械再通后颅内出血转化模型的建立

Hemorrhagic transformation induced by mechanical reperfusion and acute hyperglycemia in a rat ischemic model

目的 建立模拟急性缺血性卒中血管内机械再通治疗后颅内出血转化（-HT）的动物模型.方法 通过诱发高糖血症联合线栓法闭塞大鼠大脑中动脉5h再通的方法,观察血管再通19 h后大鼠HT的情况.结果 24只模型组大鼠在基底节和皮层出现不同程度HT,以脑实质血肿为主.联合多次高糖注射比单次高糖注射更易形成HT[88.5 （23/26）比25.0（1/4）,P＜0.05].血管再通后闭塞侧血脑屏障破坏,脑组织中基质金属蛋白酶（MMP）-9蛋白较假手术组明显表达（0.65±0.06比0.37±0.13,P＜0.01）,而基底膜胶原酶（Collagen）Ⅳ表达较假手术组减少（0.48 ±0.10比0.84±0.08,P＜0.01）.结论 多次高糖注射诱发大鼠高糖血症联合线栓法闭塞大脑中动脉5h后再通的方法可成功模拟血管内机械再通治疗后HT的发生.

Objective To investigate an ideal animal model for hemorrhagic transformation （HT） after mechanical thrombectomy for acute ischemic stroke with large-vessel occlusion.Methods Hemorrhagic transformation was examined by 5 h transient middle cerebral artery occlusion and 19 h reperfusion combined with hyperglycemia induced by injection of 50% glucose.Results We found that 80% animals in the experimental group had HT in the basal ganglia and cerebral cortex.Most of HT was the kind of parenchymal hematoma.HT occurred more frequently in the group of multiple injection of high glucose than in the group of single injection of high glucose [88.5 % （23/26） vs.25.0% （1/4）,P 〈 0.05].Blood-brain barrier permeability was increased in the ischemic-reperfusion hemisphere.The expression of matrix metalloproteinase-9 was increased in the ipsilateral hemisphere （0.65 ± 0.06 vs.0.37 ± 0.13,P 〈 0.01）,and that of collagen type Ⅳ decreased （0.48 ±0.10 vs.0.84 ±0.08,P〈0.01）.Conclusion HT following endovascular mechanical thrombectomy can be successfully simulated by transient middle cerebral artery occlusion for 5 h combined with hyperglycemia induced by multiple injection of high glucose in rats.