Objective To investigate the influence of poly(ADP-ribose)polymerase inhibitor PJ34 on blood brain barrier(BBB)in rats with cere-bral ischemia-reperfusion injury. Methods Rat model of cerebral ischemia-reperfusion injury was established by the middle cerebral artery occlu-sion. A total of 135 SD rats were randomly divided into 3 groups:sham-operated group(sham group),ischemia-reperfusion group(IR group)and PJ34 group(PJ34 group). 45 animals in each group were then equally divided into subgroups and the rats were sacrificed at 6 h,24 h,48 h after re-perfusion,respectively. BBB permeability was evaluated by detection of extravasated Evans blue(EB). The expression of tumor necrosis factorα(TNF-α)and matrix metalloproteinase 9(MMP-9)activity were measured by immunohistochemistry and western blot at different time points. Re?sults Compared with sham group,the contents of EB and the expressions of TNF-αand MMP-9 in IR group were increased significantly(P<0.05). Compared with IR group,the contents of EB and the expressions of TNF-αand MMP-9 in PJ34 group were markedly decreased at the same time point(P<0.05). Conclusion The present study provided in vivo evidence that PARP inhibitor PJ34 can protect against cerebral ischemia re-perfusion injury,and the mechanism might be related to maintaining the stability of blood-brain barrier by suppressing the expression of TNF-αand MMP-9 in ischemic cortex.%目的 探讨PARP-1抑制剂PJ34对大鼠局灶脑缺血再灌注损伤后血脑屏障的影响.方法 线栓法建立大鼠局灶性脑缺血再灌注模型,135只大鼠随机分为假手术组(sham组)、缺血再灌注模型组(IR组)、PJ34干预组(PJ34组),每组45只,每组大鼠再随机分为3个亚组,分别在再灌注6、24和48 h时间点处死.测定伊文思蓝(EB)含量,观察脑组织血脑屏障通透性.免疫组织化学及western bolt方法观察缺血侧皮层肿瘤坏死因子α(TNF-α)的表达和基质金属蛋白酶9(MMP-9)的活性变化.结果与sham组比较,IR组大鼠EB含量、TNF-α及MMP-9的表达明显升高(P<0.05);与IR组比较,PJ34组EB含量、TNF-α及MMP-9表达水平明显降低(P<0.05).结论 PARP-1抑制剂PJ34对大鼠脑缺血再灌注损伤后血脑屏障有一定的保护作用,其作用机制与降低缺血侧皮层TNF-α、MMP-9的表达水平,维持血脑屏障的稳定性有关.
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