局灶性脑缺血/再灌注损伤后大鼠脑组织tPA表达变化与细胞凋亡研究

Expression of tPA and apoptosis following focal cerebral ischemia/reperfusion injury in rats

目的 探讨大鼠脑缺血 /再灌注后脑组织内组织型纤溶酶原激活物 (t PA)表达变化及与细胞凋亡的关系和意义。方法 采用大鼠局灶性脑缺血 /再灌注模型 ,应用免疫组化染色及原位杂交技术检测脑组织 t PA表达变化 ,TU NEL 染色观察神经元的凋亡及其发生规律。结果 t PA蛋白及 m RNA在缺血再灌注早期即开始表达 ,主要见于皮质损伤区周围及海马区 ,阳性着色的神经元表达明显 ,血管表达较弱。再灌注 4 8h神经元表达明显增强 ,缺血灶及其周边的微血管内皮表达也明显增强。再灌注 72 h表达有所下降。凋亡细胞主要出现于大脑皮质及尾壳核病变中心区的周围 ,再灌注 4 8～ 72 h达高峰。结论 脑缺血 /再灌注损伤可诱导神经元及血管内皮细胞 t PA表达增加 ,t PA可能通过促进细胞凋亡而介导再灌注损伤。

Objective To explore the expression of tissue plasminogen activator (tPA) and tPA mRNA following cerebral ischemia/reperfusion injury in rat brains. Methods MCAO/R was induced using the filament occlusion method. The samples were analyzed by immunohistochemical methods and in situ hybridization. Apoptotic neurons were detected by TUNEL. Results Expression of tPA increased after MCAO/R in every group of rats with ischemia/reperfusion injury and increased significantly during 48h after reperfusion. Positive staining neurons of tPA were detected at both the regions of ischemia in the cortex and the hippocampus of the same hemisphere. Meanwhile, positive staining of tPA in endothelial cell increased evidently. Apoptotic neurons were detected mainly at the regions of the border of ischemic core and reached its peak during 48～72h after reperfusion.Conclusion Expression of tPA in neurons and endothelial cells may be induced after ischemia/reperfusion injury. Ischemia/reperfusion injury may be mediated by tPA through its function of promotion of apoptosis.