实验性汞中毒小脑变性的病理观察(英文)

Chronological changes of pathology in cerebellar degeneration in rats with methylmercury induced toxication

目的:探讨氯化甲基汞(MMC)中毒大鼠小脑变性的病理改变及机制。方法:本研究在大鼠服用MMC4mg/(kg·d)所致的亚急性汞中毒模型上,分别在服用MMC后第11、15、18和21天断头,采用组织和免疫病理技术动态观察小脑的病理演变,并采用TUNEL染色观察细胞凋亡改变,同时在电镜下观察了超微结构改变。结果:在服用MMC第18天,TUNEL染色显示小脑颗粒细胞有散在的凋亡细胞,主要位于脑回深部近白质区的颗粒层。第21天,凋亡细胞明显增加,颗粒细胞减少。MRF-1染色可见大量的小胶质细胞反应,GFAP示胶质细胞增生明显,而Purkinje细胞则保留完整。服用MMC第18天的超微结构观察表明,细胞核皱缩,体积缩小,形态不规则,电子密度增高,可见密集深染的染色质,部分细胞核破碎,呈现为均一深染的泪珠状染色质,符合凋亡改变。结论:本研究结果表明汞中毒的小脑变性的病理机制为细胞凋亡,其病理变化符合人类汞中毒表现。

Objective: To explore the pathology and pathogenesis of cerebellar injuries induced by methylmercury chloride(MMC) toxication in rats. Methods: Rats were given MMC(4 mg·kg -1·d -1) consecutively and sacrificed on days 11, 15, 18 and 21. Pathological changes of the cerebellum were observed by histo-immunopathology; in situ staining was performed for DNA strand breaks in cerebellar granule cells by TUNEL technique; and the ultrastructures were observed by electron microscope. Results: On day 18, sparse TUNEL positive granular cells were observed mainly in deep lamina adjacent to the white matter. On day 21, apoptotic cells markedly increased and granule cells decreased with well-preserved Purkinje cells. Immunostaining with MRF-1 and GFAP demonstrated severe microgliosis and astrocytosis. On day 18, electron microscopy demonstrated that the nuclei of MMC-treated animals were shrunken and displayed increased electron density, and some homogeneously dense nuclear chromatin with tear-drop features, which were compatible with the apoptotic changes. Conclusion: These results indicate that the pathological changes in the cerebellum in this subacute MMC intoxication model resemble human cases, and the degeneration of granule cells is apoptosis.