摘要
目的探讨组织纤维蛋白溶酶原激活剂(tPA)在新生大鼠缺氧缺血性脑损伤(HIBD)中的作用。方法选用7日龄Wistar新生大鼠,应用Vannucci动物模型造模法制备新生大鼠HIBD模型。采用反转录酶-聚合酶链反应(RT-PCR)、脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)、双重免疫荧光、免疫印迹方法检测tPA在脑缺血缺氧急性期大鼠脑组织的表达及神经细胞凋亡、血脑脊液屏障损伤情况。结果HIBD新生大鼠内源性tPA表达明显增加。tPA活性增加可致血管周围的层黏连蛋白、内皮紧密连接蛋白降解,加重血脑脊液屏障破坏。随着缺血再灌注时间的延长,大脑凋亡细胞也逐渐增加。结论tPA表达的增加在脑缺氧缺血急性期可有助于血栓溶解,但其蛋白水解作用在脑缺氧缺血亚急性期却可导致神经细胞凋亡,血脑脊液屏障破坏加重,进而造成脑损伤加重。
Objective To explore the role of tissue - type plasminogen activator （tPA） in neonatal rat with hypoxia - ischemia brain damage （HIBD）. Methods Seven - day - old Wistar rat pups were used for the Vannucci model of HIBD. Reverse transcription - polymerase chain reaction （RT- PCR）, terminal deoxynucleotidyl transferase mediated dUTP nick end labeling （TUNEL）, double immunostaining and immunoblot analysis were adapted to determin the expression of tPA at acute phase after HIBD and neural cell apoptosis and the blood - brain - harrier （BBB） damage. Results Neonatal hypoxia - ischemia triggers persistent induction of the plasminogen system. The increase of tPA activity induced the degradation of laminin and occludin which would aggravate the BBB damage. The number of neural cell apoptosis after HIBD increased progressively with the reperfusion time. Conclusions The increase of tPA at the acute phase after HIBD can help clot to dissolve, while its extravascular proteolysis will induce cell apoptosis and BBB damage which will aggravate brain injury.
出处
《实用儿科临床杂志》
CAS
CSCD
北大核心
2009年第8期622-624,共3页
Journal of Applied Clinical Pediatrics
基金
国家青年科学基金项目资助(30700908)
