实验性汞中毒大鼠周围神经损伤的机制

Mechanism of peripheral nerve injury in rats induced by methylmercury intoxication

目的:观察慢性汞中毒大鼠行为学和组织中汞含量变代,探讨慢性汞中毒周围神经的病理损伤及机制。方法:8只雄性WisterKA大鼠,随机分为实验组和对照组两组各4只,对照组正常饲养,实验组采用氯化甲基汞4mg/kg隔日灌胃,制作了大鼠亚急性汞中毒动物模型,观察了坐骨神经,脊神经节和前后神经根的病理改变。结果:对照组各项指标均正常,无行为变化。服药第21天,实验组动物出现神经系统损害症状,表现为步态不稳,体质量由服药前(267.0±6.0)g降至(253.0±4.5)g。苏木精-伊红、Bodian及KB染色均显示坐骨神经纤维弯曲、断裂、呈空胞样改变,并见多个髓磷脂小球。甲苯胺兰染色示神经纤维数量减少,可见多个高电子密度的有髓纤维,髓鞘及轴索破坏。NF-200免疫组化染色显示轴索断裂,成块状深染及空胞化。ED-1染色可见神经组织内有大量的单核吞噬细胞浸润。神经剥离的单个纤维,光镜下可见神经轴索断裂成块状,而髓鞘相对完整。脊髓后根明显变性,前根未见明显的变化。脊神经节内神经纤维呈现明显的变性,但神经节细胞保留完好。结论:亚急性汞中毒最早的病理变化发生在周围神经轴索,表现为原发性轴索变性,可能与汞中毒干预了细胞的代谢有关。

AIM:To observe the changes of praxiology and mercury content in the tissue of rats with chronic methylmercury intoxication,and explore the pathological injury of peripheral nerve caused by methylmercury chloride(MMC) intoxication and the mechanism. METHODS:Eight male Wister KA rats were randomly divided into experimental group(n=4) and control group(n=4),rats in the control group were fed normally,rat models of subacute methylmercury intoxication was made by gastric perfusion of MMC 4 mg/kg every other day.The pathological changes of sciatic nerve, spinal ganglion,ventral and dorsal roots in rats were observed. RESULTS:Normal indexes and no praxiological changes were observed in the control group.On the 21st day,the initial signs of hind leg ataxia developed in the experimental group,and the body mass was reduced from(267.0±6.0) g to(253.0±4.5) g.Nerve fibers in sciatic nerve were beaded,fragmented and vesicular in appearance,and numerous myelin ovoids were observed by using HE,KB and Bodian staining.Toluidine blue staining demonstrated loss of myelinated fibers, numerous highly electron dense myelinated fibers and destruction of both axons and myelins.NF 200 immunohistochemical staining illustrated that the degenerated nerve fibers had a segmented,vesicular appearance.ED 1 monoclonal antibody indicated that there were numerous macrophages in the nerve fibers.The teased fiber showed a fragmented axon with preserved myelin sheath.Dorsal roots had a obvious degeneration,in contrast,the ventral roots were well preserved.In spinal ganglion, nerve fibers had similar degenerative changes as seen in the dorsal roots but ganglion cells were preserved well. CONCLUSION:The earliest pathological change of sub acute MMC intoxication occurs in peripheral nerve axon,and manifests primary axonal degeneration,which is possibly related with the intervention of cellular metabolism by MMC intoxication.