大鼠脑缺血后PEDF表达及替米沙坦调控作用的研究

摘要

目的 动态观察大鼠脑缺血后色素上皮源性生长因子(PEDF)的表达变化,并探讨替米沙坦的调控机制.方法 线栓法建立大脑中动脉闭塞(MCAO)大鼠模型.实验1,动态观察PEDF蛋白和基因表达;实验2,替米沙坦干预,采用Western blot和qR-T PCR观察PEDF基因和蛋白变化,比较各组脑梗死体积、患侧脑水肿和神经功能.结果 MCAO后24h开始,PEDF表达明显减少.替米沙坦通过激活过氧化物酶体增殖物激活受体γ(PPARγ)上调PEDF,明显改善神经功能缺失,减轻脑水肿,减小梗死体积.结论 调控内生性PEDF表达可能是治疗脑缺血的新靶点.%Objective This study is to evaluate the time course expression of PEDF and explore the underling regulation mechanisms of telmisarlan. Methods Male Sprague -Dawley rats were subjected to permanenl middle cerebral artery occlusion ( MCAO). Experiment 1: The time course expression of PEDF protein and gene was evaluated. Experiment 2: Telmisartan was sysLemically administered to explore the effect on PEDF at 24 h after cerebral ischemia by wesLern blot and qRT -PCR. The neurological deficits, brain water content and infarct volume were measured. Results Telmisartan dramatically up -regulaLed PEDF, alleviated the neurological deficits, brain water content and infarct volume in PPARγ -dependent way. Conclusion The regulation of intrinsic PEDF may be one of the strategic targets for cerebral ischemic therapies.