纳米二氧化钛暴露的神经毒性作用及机制

The neurotoxic effects and mechanisms of titanium dioxide nanoparticles

以多巴胺能神经细胞SH-SY5Y和PC12为实验模型,深入探讨了不同晶型(锐钛矿型、金红石型、混合型)和不同粒径(25,50,100nm)的纳米二氧化钛(TiO_(2)-NPs)暴露对多巴胺能神经细胞的毒性影响及机制.结果表明,金红石型TiO_(2)-NPs暴露具有更强的毒性作用,其次是混合型和锐钛矿型.此外,粒径较小的TiO_(2)-NPs对神经细胞的毒性更显著,特别是25nm粒径的TiO_(2)-NPs,其神经毒性作用与诱导活性氧自由基生成和细胞凋亡相关.蛋白免疫印迹法发现,TiO_(2)-NPs能上调Bax和细胞色素C的水平,下调Bcl-2的表达,同时激活Caspase-3,表明TiO_(2)-NPs通过影响线粒体凋亡途径相关蛋白的表达诱导多巴胺能神经细胞凋亡.

The toxicological effects and mechanisms of different crystal forms (anatase,rutile,mixed) and particle sizes (25,50,100nm) of titanium dioxide nanoparticles (TiO_(2)-NPs) on dopaminergic cells were thoroughly investigated using SH-SY5Y cells and PC12 cells as experimental models.The results showed that rutile TiO_(2)-NPs exhibited pronounced toxic effects,followed by mixed and anatase TiO_(2)-NPs.Furthermore,smaller particle sizes were associated with greater toxicity to nerve cells,particularly at 25nm.The neurotoxicity was related to the induction of reactive oxygen species (ROS) generation and apoptosis.The Western Blotting analysis revealed that TiO_(2)-NPs upregulated the levels of Bax and Cytochrome C,downregulated the expression of Bcl-2,and activated Caspase-3,indicating that TiO_(2)-NPs induced apoptosis of dopaminergic cells by affecting the expression of proteins related to mitochondrial apoptosis pathway.