脑缺血再灌注早期L-NAME的脑保护机制研究

目的通过L-硝基-精氨酸甲酯(L-NAME)对大鼠脑缺血再灌注损伤早期MMP-9、GFAP动态表达及与血脑屏障形态、功能关系的研究,探讨脑缺血再灌注早期L-NAME的脑保护机制。方法 108只SD大鼠随机分为3组:假手术组,损伤组,L-NAME治疗组。干湿重法测定缺血脑组织含水量,伊文思蓝测定血脑屏障通透性,免疫组织化学技术检测脑组织的MMP-9蛋白、GFAP蛋白的表达,电镜研究血脑屏障超微结构。结果脑缺血再灌注损伤后大脑皮质的神经细胞线粒体肿胀或溶解;脑毛细血管周围出现空泡化,内皮肿胀,基底膜厚薄不均。脑缺血再灌注损伤后脑含水量和EB含量明显增高,MMP-9、GFAP表达升高,差异具有统计学意义。L-NAME治疗后,脑含水量和EB含量明显下降,MMP-9、GFAP表达恢复至正常水平,脑毛细血管、神经细胞、突触及基底膜等超微结构基本恢复正常。结论 L-NAME对脑缺血再灌注损伤早期具有明显的保护作用,其机制与抑制MMP-9、GFAP表达,清除自由基和调节星形胶质细胞适度增生有关。

Protective effect of L-NAME against cerebral ischemia-reperfusion injury in early stage

Objective To explore the effect of L-NAME on dynamic expression of matrix metalloproteinase(MMP-9),glial fibrillary acidic protein(GFAP),morphology and function of blood-brain barrier in rats of cerebral ischemia-reperfusion injury in early stage.Methods One hundred and eight rats were randomly assigned to sham operation group,injury group and L-NAME group.Brain water content was detected by calculating dry/wet weight.The permeability of blood-brain barrier(BBB) was observed with Evans blue under electron microscope.The changes of brain MMP-9 and GFAP expression were determined by immunohistochemical method.Results Under transmission electron microscope,mitochondrion of some neurons of the cerebral cortex were swollen or dissolved in injury group,with vacuolated,swollen endothelium,abnormity of capillary basement membranes of BBB.Brain water content and brain Evan’s blue content were significantly increased after ischemia/reperfusion injury.Expression of brain MMP-9 and GFAP in injury group was higher than that in sham operation group(P<0.05).Brain water content and brain Evan’s blue content decreased in L-NAME group,changes of ultrastructure with severe injury nearly returned to the normal,and the expression of MMP-9 and GFAP was also returned to the basal level.Conclusion L-NAME may have obvious protective effects against the early stage cerebral ischemia-reperfusion injury by adjusting the activity of astrocytes,scavenging free radical,and inhibiting the expression of MMP-9 and GFAP.