Objective To investigate the effects of PJ34,a poly ADP-ribose polymerase(PARP)inhibitor,on the expression of matrix metallopro-teinases-9( MMP-9 )and Claudin-5 in ischemic cortex of rats with focal cerebral ischemia-reperfusion(I/R)injury. Methods The focal cerebral ischemia-reperfusion model of middle cerebral artery occlusion(MCAO)was established by intraluminal suture . PJ34 was injected intraperitoneal-ly. Blood-brain barrier(BBB)permeability was quantitatively determined by Evans blue assay. Infarct volume changes were observed by 2,3,5-tri-phenyltetrazolium chloridedyeing(TTC)staining. The expression of the MMP-9 and Claudin-5 in rats of cerebral cortex were measured by immuno-histochemistry assay and western blot analysis . Results Compared with sham group,the expression of MMP-9,the contents of EB and infarct vol-ume increased progressively over time after I/R,and reached maximum levels at 48 h(P<0.05);The expression of Claudin-5,the contents of EB and infarct volume reduced significantly over time after I/R,and reached the minimum levels at 48 h in model group(P<0.05). Compared with model group,the expression of MMP-9,the contents of EB and infarct volume was reduced significantly and the expression of Claudin-5,the con-tents of EB and infarct volume was increased at the same time point in PJ34 group(P<0.05). Conclusion PJ34 maintained the blood-brain barri-er permeability by inhibiting the expression of MMP-9,and increasing the expression of Claudin-5,which had neuroprotection on cerebral ischemia-reperfusion injury.%目的 探讨多聚ADP核糖聚合酶1(PARP-1)抑制剂PJ34对大鼠局灶性脑缺血再灌注后缺血侧皮层金属蛋白酶9(MMP-9)和Claudin-5表达的影响.方法 采用线栓法制备大鼠局灶脑缺血再灌注模型,腹腔注射PJ34,用伊文思蓝(EB)法检测血脑屏障通透性变化,采用2,3,5-三氨基苯甲四氮唑(TTC)染色检测脑梗死体积变化,免疫组化和western blot方法检测脑缺血侧皮层MMP-9和Claudin-5表达.结果 与假手术组比较,随缺血再灌注时间延长,模型组MMP-9表达、EB含量、脑梗死体积逐渐增加,48 h达峰;Claudin-5的表达、EB含量、脑梗死体积逐渐减少,48 h最低(P均<0.05).与模型组比较,PJ34组MMP-9表达、EB含量、脑梗死体积在各个时间点明显降低,Claudin-5的表达、EB含量、脑梗死体积在各个时间点明显增高(P均<0.05).结论PJ34通过抑制MMP-9的表达,增加Claudin-5的表达来维持血脑屏障通透性,对脑缺血再灌注损伤有神经保护作用.
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