Wistar大鼠实验性自身免疫性脑脊髓炎轴索损害的病理学分析

Pathological findings of axonal injury in a rat model of experimental allergic encephalomyelitis

目的在建立Wistar大鼠实验性变态反应性脑脊髓炎(EAE)动物模型基础上探讨多发性硬化的病理变化,尤其针对轴索损害的特点进行深入探讨。方法对EAE大鼠的脑和脊髓进行HE染色、LFB髓鞘染色和Bielschowsky染色,分别以间接免疫荧光方法双染标记非磷酸化神经丝蛋白(SMI-32)和髓鞘碱性蛋白(MBP)MBP,以及轴索淀粉样前体蛋白(APP)和MBP。结果脑和脊髓组织内可见大量炎细胞浸润形成典型的袖套改变,伴有大片状脱髓鞘,轴索结构排列紊乱,呈空泡样缺失。SMI-32染色证明发病14 d脊髓白质内出现大量非磷酸化的神经丝蛋白,可见APP堆积形成轴突卵形体。表明发病早期即出现了明显的轴索损害,且髓鞘脱失和轴索损害的发生不同步。结论 EAE大鼠不同发病阶段出现不同程度的炎症反应,发病高峰期的炎症浸润最明显。EAE的轴索损害开始于疾病的早期阶段,并不断进展。

Objective To observe the pathological changes of axonal injury in a rat model of experimental allergic encephalomyelitis（EAE）.Methods With HE,luxol fast blue and Bielschowsky staining,the expression of APP,MBP,SMI-32 and MBP in the brain and spinal cord of EAE rats using double-labeling indirect immunofluorescence.Results Extensive cuffing lesions of inflammatory cell infiltrations were found in the brain and spinal cord of the rats,accompanied by multiple lesions of demyelination,axonal disarrangement with vesicular loss.SMI-32 staining identified numerous nonphosphorylated neurofilament,indicating the presence of axonal injury.Axonal oval bodies formed by APP accumulation were found in the white matters of the spinal cord 14 days after EAE,suggesting that neuraxial damage occurred in the early stage of EAE which was not synchronous with myelin loss.Conclusion Different levels of inflammation occur in different stages of EAE,and inflammatory cell infiltration is the most obvious at the peak of EAE.Axonal injury occurs in the early stage of EAE and progresses over the entire disease course.