脑梗死潜在溶栓治疗时间窗实验研究

The experimental study on potential thrombolytic therapeutic time window for rat cerebral infarction

目的 观察缺血脑组织动态病理改变 ,探索大鼠脑梗死潜在溶栓治疗时间窗。方法 采用光镜、电镜、免疫组化 ,辅以图像分析系统 ,对大鼠大脑中动脉闭塞 (MCAO)后缺血脑组织内神经元、胶质细胞、微血管内皮细胞病理改变及白细胞浸润情况进行动态 (MCAO后 10min～ 7d)观察和量化分析。结果 MCAO 6h内 ,缺血脑组织表现为局灶性可逆性病理改变。MCAO 12h ,出现不可逆性病理改变 ,病变累及整个大脑中动脉供血区。MCAO <12h组与MCAO≥ 12h组大鼠脑梗死体积存在显著性差异 (t=3.32 9,P =0 .0 0 2 5 )。结论 大鼠大脑中动脉闭塞后 ,潜在的最长溶栓治疗时间窗为 6～ 12h。

Objective To explore the potential therapeutic time window for rats with permanent middle cerebral artery occlusion (MCAO), by observing the dynamic pathologic alterations of ischemic cerebral tissue. Methods 185 male Wistar rats were divided into 19 experimental groups with different ischemic intervals and controlling groups. The rat ischemic cerebral models were made with the ischemic time from 10 min to 7 days. Light microscope, electron microscope, image analysis system and immunohistochemical method were used to observe and detect the pathologic and morphologic alterations of ischemic neurons, glial cells, endothelial cells of microvessels and infiltration of white cells in the ischemic regions. Results In 6 hours after MCAO, the pathologic alterations were reversible including vacuolation in neuropil, neuronal scalloping, swelling of perikarya and disintegration of glial cells. 12 hours after MCAO, the extent extended to the whole area feeded by MCA with irreversible pathologic alterations, such as cytoplasmic eosinophil affecting both neuronal and glial cells and formation of ghosts. 12 hours after MCAO, the volume of lesion covered over 50% of the ipsilateral hemisphere. There were significant differences in the volume of lesions between the rats with the ischemic time less than 12 hours and more than 12 hours ( t=3.329,P=0.0025 ). Conclusions The potential thrombolytic therapeutic time window in rats is 6～12 hours after MCAO.