实验性变态反应性脑脊髓炎发病初期血脑屏障的变化及基质金属蛋白酶的作用研究

目的:探讨多发性硬化的动物模型-实验性变态反应性脑脊髓炎(EAE)发病初期血脑屏障(BBB)的变化及基质金属蛋白酶(MMPs)的作用机制。方法:建立Wistar大鼠EAE动物模型,取发病初期未出现临床症状的EAE大鼠,取脊髓组织通过共聚焦显微镜观察伊文思兰在BBB中的通透性,并用免疫组化的方法测定免疫球蛋白(IgG)的沉积和基质金属蛋白酶(MMPs)的分布。探讨发病初期BBB的变化。结果:CM观察发现,未发病的EAE大鼠沿脊膜下有桔红色荧光分布,同样,EAE大鼠脊髓切片可见有IgG渗出,表现为神经纤维网和神经胶质细胞胞浆呈棕褐色染色,MMP9,-2在脊膜和血管内皮细胞内呈阳性表达,而对照组均呈阴性表达。结论:BBB在EAE发病初期已经受损,MMPs是BBB破坏的重要因素,有降解血管基底膜的作用,可促使炎细胞侵入中枢神经系统。

The perrfieability change of BBB in the early stage of EAE and the pathogenesis of MMPs in the destruction of BBB

Objective:To investigate the permeability change of BBB in the early stage of EAE and the pathogenesis of MMPs in the destruction of BBB. Method: The animal model was established in Wistar rat, the permeation of EB in BBB in early stage of EAE was observed through the confocal microscopy (CM). the deposit of IgG and distribution of MMPs were determined by means of IHC. Results: We can see diffuse extravasation of EB in the underlying pia mater in asymptomatic EAE rat, mild IgG effusion in the perivascular part of spinal cord segments and MMP-2, -9 were expressed in cytoplasm of spinal meninges cells and microgliocyte. Conclusion: BBB were damaged in the early stage of EAE, MMPs can degrade the basal lamina of blood vessel and played the main role in the BBB damage, which can precipitate the inflammatory cells to intrud into centry nervous system.