脂氧素A4对局灶性脑缺血再灌注大鼠血脑屏障通透性的影响

Effect of lipoxin A4 on permeability of blood-brain barrier after focal cerebral ischemia-reperfusion in rats

目的 探讨脂氧素A4对局灶性脑缺血再灌注大鼠血脑屏障通透性的影响.方法 健康成年雄性SD大鼠54只,体重200～250 g,随机分为3组（n=18）：假手术组（S组）、局灶性脑缺血再灌注组（I/R组）和脂氧素A4组（L组）.采用改良线栓法制备大鼠局灶性脑缺血再灌注损伤模型,阻断右侧大脑中动脉缺血2 h后行再灌注.L组缺血即刻右侧侧脑室注射脂氧素A4 100 ng,S组和I/R组右侧侧脑室注射等容量生理盐水5 μl.于再灌注24 h时行神经功能缺陷评分,静脉注射2%伊文斯蓝4 ml/kg,1 h后处死大鼠取脑,测定右侧脑水含量和伊文斯蓝含量,检测脑皮质基质金属蛋白酶9（MMP-9）的表达.结果 与S组比较,I/R组和L组神经功能缺陷评分、脑水含量和伊文斯蓝含量升高,脑皮质MMP-9表达上凋（P＜0.05或0.01）;与I/R组比较,L组神经功能缺陷评分、脑水含量和伊文斯蓝含量降低,脑皮质MMP-9表达下调（P＜0.01）.结论 脂氧素A4可降低血脑屏障通透性,减轻脑水肿,促进局灶性脑缺血再灌注损伤大鼠的神经功能恢复,其机制与抑制MMP-9表达上调有关.

Objective To investigate the effect of lipoxin A4 （ LXA4 ） on the permeability of blood-brain barrier （BBB） after focal cerebral ischemia-repeffnsion （I/R） in rats. Methods Fifty-four adult male SD rats weighing 200-250 g were randomly divided into 3 groups （ n = 18 each）： group Ⅰ sham operation （group S）; group Ⅱ focal cerebral I/R （ group I/R） and group Ⅲ LXA4 （ group L）. Focal cerebral I/R was produced by middle cerebral artery occlusion （MCAO） with a 4-0 nylon thread with rounded tip inserted into right internal jugular vein and threaded cranially in group Ⅱ and Ⅲ . In group Ⅲ LXA4 100 ng was injected into right lateral ventricle of the brain after MCA was successfully occluded. MCAO was maintained for 2 h. The neurological deficit was evaluated and scored （0 = no deficit, 5 = death） at 24 h of reperfusion. 2% Evans blue 4 ml/kg was injected via femoral vein at 1 h before the animals were sacrificed. The animals were killed and their brains were immediately removed for determination of brain water content, Evans blue content and expression of matrix metalloproteinase-9 （MMP-9）in the ischemic cortex. Results The neurologic deficit scores, the brain water and Evans blue content and MMP-9 protein expression in the cortex were significantly higher in I/R group than in S group. The cerebral I/R-induced changes were significantly attenuated in LXA4 group. Conclusion LXA4 can protect blood-brain barrier against cerebral I/R injury by inhibiting MMP-9 protein expression in the brain tissue.