L-硝基-精氨酸甲酯对大鼠脑缺血再灌注损伤后血脑屏障功能和基质金属蛋白酶-9表达的影响

目的:观察L-硝基-精氨酸甲酯(L-NAME)对大鼠脑缺血再灌注损伤后血脑屏障功能和MMP-9表达的影响,探讨其对脑缺血再灌注损伤的保护作用及其机制。方法:将60只SD大鼠随机分为3组:1假手术组;2对照组;3L-NAME治疗组。用线栓法制作大鼠脑缺血再灌注模型,再灌注48h后干湿重法测定缺血脑组织含水量,用伊文思蓝测定血脑屏障通透性,免疫组织化学技术检测MMP-9的表达,同时电镜观察血脑屏障的变化。结果:脑缺血再灌注48h,对照组缺血侧脑含水量明显升高,EB含量也明显增加,电镜观察发现血脑屏障破坏严重,MMP-9的表达也较假手术组显著增加;而应用L-NAME处理的大鼠其缺血脑组织含水量明显减少,缺血侧EB含量较对照组也明显降低(P<0.05),同时电镜观察到血脑屏障的破坏减轻,而MMP-9表达水平也明显低于对照组。结论:L-NAME对大鼠脑缺血再灌注损伤后的血脑屏障具有保护作用,其作用机制可能是通过抑制MMP-9表达来实现的。

Effects of L-NAME on blood-brain barrier permeability and MMP-9 expression after cerebral ischemia and reperfusion injury in rats

Objective： To investigate the effects of L-NAME on blood-brain barrier of cerebral ischemia and reperfusion in rats,and explore the possible mechanisms. Methods： 60 normal male SD rats were divided randomly into 3 groups：（1）Sham-operation （n = 20）; （2）Control （n= 20）;（3）L-NAME （n = 20）. Rat cerebral ischemia and reperfusion model was established by the method of thread inserting right middle cerebral artery occlusion（MCAO）, The brain water content was measured 48 h after reperfusion. At the same time,The permeability of blood-brain barrier was observed with electron microscope and by detecting the content of Evans Blue leaked out the brain tissue of ischemic side. The expression of MMP-9 in different groups was dtected by immunohistochemical method. Results： 48 h after crebral ischemia and reperfusion injuriy, the content of brain water and Evans Blue leaked out increased obviously, The breakdown of blood-brain barrier was severe the expression of MMP-9 also increased obviously. However, L-NAME can subtract the content of brain edema and Evans blue（P〈0.05）, relieve the breakdowm of blood-brain barrier on electron microscope. The expression of MMP-9 were decreased in L-NAME group contrasted with control group（P〈0.05）. Conclution： L-NAME has the protective effects on BBB in the model of cerebral ischemia and reperfusion injury. The mechanisms may be by restrainning the expression of MMP-9.