摘要
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。
Objective To investigate the effects ofPJ34, a poly ADP-ribose polymerase （PARP） inhibitor, on the expression of matrix metallopro teinases-9 （ MMP-9 ） and Claudin-5 in isehemic cortex of rats with focal cerebral isehemia-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 intraperitoneally. Blood-brain barrier （ BBB ） permeability was quantitatively determined by Evans blue assay. Infarct volume changes were observed by 2,3,5-hi- phenyltetrazolium ehloridedyeing （TTC） staining. The expression of the MMP-9 and Claudin-5 in rats of cerebral cortex were measured by immunohistochemistry assay and Western blot analysis. Results Compared with sham group, the expression of MMP-9, the contents of EB and infarct volume increased progressively over time after I/R, and reached maximum levels at 48 h （P 〈 0.05 ） ; The expression of Clandin- 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 contents of EB and infarct volume was increased at the same time point in PJ34 group （P 〈 0.05 ）. Conclusion PJ34 maintained the blood-brain barrier permeability by inhibiting the expression of MMP-9, and increasing the expression of Claudin-5, which had neuroprotection on cerebral isehemiareperfusion injury.
出处
《中国医科大学学报》
CAS
CSCD
北大核心
2015年第8期694-698,703,共6页
Journal of China Medical University
基金
辽宁省自然科学基金(201102074)
