CAJ | 학술논문

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.
목적 탐토지양소A4대국조성뇌결혈재관주대서혈뇌병장통투성적영향.방법 건강성년웅성SD대서54지,체중200～250 g,수궤분위3조(n=18):가수술조(S조)、국조성뇌결혈재관주조(I/R조)화지양소A4조(L조).채용개량선전법제비대서국조성뇌결혈재관주손상모형,조단우측대뇌중동맥결혈2 h후행재관주.L조결혈즉각우측측뇌실주사지양소A4 100 ng,S조화I/R조우측측뇌실주사등용량생리염수5 μl.우재관주24 h시행신경공능결함평분,정맥주사2%이문사람4 ml/kg,1 h후처사대서취뇌,측정우측뇌수함량화이문사람함량,검측뇌피질기질금속단백매9(MMP-9)적표체.결과 여S조비교,I/R조화L조신경공능결함평분、뇌수함량화이문사람함량승고,뇌피질MMP-9표체상조(P＜0.05혹0.01);여I/R조비교,L조신경공능결함평분、뇌수함량화이문사람함량강저,뇌피질MMP-9표체하조(P＜0.01).결론 지양소A4가강저혈뇌병장통투성,감경뇌수종,촉진국조성뇌결혈재관주손상대서적신경공능회복,기궤제여억제MMP-9표체상조유관.
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.