氯化甲基汞中毒大鼠周围神经损伤的病理演变

Chronological changes of pathology in peripheral nervous system in rats exposed to methylmercury intoxication

目的 :探讨氯化甲基汞中毒大鼠周围神经损伤的病理改变及病理机制。 方法 :在 WKAH大鼠服用氯化甲基汞 4mg/ d所致的亚急性汞中毒模型上 ,采用组织病理、免疫组化、蛋白印迹等方法动态观察坐骨神经和后根神经节的病理演变 ,TU NEL 染色观察细胞凋亡。 结果 :中毒后第 11天后根神经节内可见散在大型神经元 A被吞噬细胞浸润 ,电镜下 A型神经元胞质内线粒体变性 ;坐骨神经远端轻微轴索变性 ,病变逐渐加重并向心性发展。第 15天开始出现髓鞘崩解 ,MRF- 1染色显示有少量的吞噬细胞反应。第 18天出现明显轴索变性及髓鞘崩解 ,可见大量浸润的吞噬细胞 ;后根神经节内 A型神经元近于消失 ,但 B型神经元保留良好 ,B型神经元的上行终末胶状质下区亦出现明显变性。TUNEL 染色未观察到节细胞凋亡。采用Western印迹法观察到坐骨神经及后根神经节神经原纤维及髓鞘蛋白 O随中毒时间延长逐渐降低 ,在第 15天后尤为明显 ,与免疫组化结果相符合。结论 :亚急性汞中毒模型中 ,A型神经元变性可能与汞中毒损伤线粒体膜继发的能量代谢障碍有关 ;而B型神经元变性则符合逆行性死亡的过程。

Objective:To explore the pathology and pathogenesis of peripheral nerve injuries in rats induced by methylmercury(MMC) intoxication.Methods:We chronologically observed the pathological changes of sciatic nerve and dorsal root ganglion (DRG) neurons in rats exposed to MMC(4 mg·kg -1 ·d -1 ) on consecutive days;rats were sacrificed on day 11,15,18 and 21.Results:On day 11,some DRG type A neurons suffered neuronophages and showed mitochondrial degeneration.Initial axonal degeneration occurred predominantly in the distal portions of sciatic nerve,and advanced proximally toward the nerve cell body.Myelin started to degrade,and MRF-1 positive macrophages appeared on day 15.On day 18,the sciatic nerve was severely degenerated with numerous macrophages infiltration.Type A neurons in DRG almost disappeared,while type B neurons were well preserved.The ascending ends of type B neurons in the substantia gelatinoa also degenerated.TUNEL did not demonstrate apoptotic cells.Immunoblotting with monoclonal antibodies PO and neurofilament demonstrated that both proteins significantly decreased from day 15.Conclusion:These results indicate that the degeneration of type A neurons is related to energy metabolism secondary to the mitochondrial membrane injuries,and type B neuron degeneration accords with a dying-back process in this subacute toxic model.