代森锰及其代谢物的神经毒性影响与机制研究

以SH-SY5Y和PC12细胞为实验模型,深入探讨了代森锰(Maneb)及其代谢产物对多巴胺能神经细胞的毒性影响与机制.结果表明,Maneb的有机部分和金属离子成分单独暴露不具有明显的毒性作用,联合暴露具有协同效应,且对细胞活性的抑制程度与同一浓度水平的Maneb相当,其原因与诱导活性氧自由基生成、细胞凋亡相关.此外,蛋白免疫印迹法发现,Maneb下调Bcl-2的表达、上调Bax、细胞色素C的水平,同时激活Caspase-3,提示线粒体凋亡途径在Maneb诱导多巴胺能神经细胞凋亡过程中的重要作用.

Neurotoxic effects and mechanisms of Maneb and its metabolites

The toxicological effects and mechanisms of Maneb and its metabolites on dopaminergic cells were investigated in depth using SH-SY5Y cells and PC12 cells as experimental samples. The results showed that the organic and metal ion components of Maneb did not have obvious toxic effects when exposed alone, but had synergistic effects when exposed in combination, and the degree of inhibition to cells viability was comparable to that of Maneb at the same concentration level. The reasons for this were related to the generation of reactive oxygen species (ROS) and apoptosis. In addition, the Western Blotting revealed that Maneb reduced the expression of Bcl-2, elevated the level of Bax and Cytochrome C and activated Caspase-3 in a dose-dependent manner, suggesting an important role of the mitochondrial apoptosis pathway in dopaminergic cells apoptosis induced by Maneb.