PJ34对脑缺血再灌注大鼠应用rt-PA后血脑屏障完整性的影响

目的　研究多聚ADP核糖聚合酶-1（poly-ADP ribose polymerase-1，PARP-1）抑制剂PJ34能否改善脑缺血再灌注大鼠应用重组人组织型纤溶酶原激活物（recombinant tissue plasminogen activator，rt-PA）后的血脑屏障完整性。 方法　将60只大鼠随机分为假手术组、缺血再灌注（ischemia-reperfusion，IR）组、rt-PA组及PJ34组。IR组：采用改良 Zea Longa 线栓法，制备局灶性脑缺血2 h再灌注模型。PJ34组及rt-PA组：缺血2 h拔出鱼线，同时给予尾静脉注射rt-PA 10 mg/kg，腹腔注射PJ34或生理盐水3 mg/kg。进行神经功能缺损评分、伊文氏蓝测定血脑屏障通透性、免疫组化分析MMP-9、Claudin-5、ZO-1的表达。 结果　rt-PA组的神经功能缺损评分、伊文氏蓝含量及MMP-9表达均高于IR组，PJ34组低于rt-PA组，但高于IR组（P<0.05）；rt-PA组的Claudin-5、ZO-1表达低于IR组，PJ34组高于rt-PA组，但低于IR组（P<0.05）。 结论　PJ34通过抑制MMP-9的表达，增加Claudin-5、ZO-1的表达，可以有效改善脑缺血再灌注后应用rt-PA的大鼠血脑屏障完整性。

Effect of PJ34 on blood-brain barrier integrity after injecting of rt-PA in rats with cerebral ischemia-reperfusion

Objective　To investigate whether the poly-ADP ribose polymerase-1 (PARP-1) inhibitor PJ34, N- (6-oxo-5,6-dihydrophenanthridin-2-yl)-2-dimethylamino can improve the integrity of the blood-brain barrier after rt-PA administration in rats with cerebral ischemia reperfusion.　Methods　Totally 60 rats were randomly divided into a sham operation group, an IR group, a rt-PA group and a PJ34 group. IR group: focal cerebral ischemia 2 h reperfusion model was made by modifying Zea Longa method. PJ34 group and rt-PA group: the fish line was removed 2 h after ischemia, rt-PA (10 mg/kg) was administered to the tail vein, and PJ34 or physiological saline (3 mg/kg) was intraperitoneally injected. The neurological function score was evaluated, the permeability of the blood-brain barrier was measured by Evans blue staining, and the expressions of MMP-9, Claudin-5 and ZO-1 was analyzed by immunohistochemistry.　Results　The mNSS score, Evans blue content and MMP-9 expression in rt-PA group were significantly higher than those in the IR group, and those in PJ34 group were lower than those in rt-PA group, but were higher than those in IR group (P＜0.05). The expression of Claudin-5 and ZO-1 in rt-PA group was lower than that in IR group, higher in PJ34 group than in rt-PA group, but lower than that in IR group (P<0.05). Conclusions PJ34 can effectively improve the integrity of blood-brain barrier of rt-PA rats after cerebral ischemia by inhibiting the expression of MMP-9 and increasing the expressions of Claudin-5 and ZO-1.