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目的:探讨百草枯致小鼠黑质细胞死亡的方式及神经毒性机制。方法:C57BL小鼠口服百草枯不同时间后采用酪氨酸羟化酶(TH)免疫组化及TUNEL法、流式细胞仪、透射电镜检测黑质部多巴胺能神经元的凋亡现象。结果:TH免疫组化及TUNEL双标染色检查示C57BL小鼠暴露于百草枯后2周后黑质部多巴胺能神经细胞即有凋亡样改变,流式细胞仪检测显示小鼠于暴露百草枯1个月时凋亡细胞数最多,与对照组相比,P<0.001;2个月时有所减少,但仍多于对照组(P<0.01)。结论:小鼠暴露于百草枯一定时间后可引起黑质部多巴胺能神经元发生凋亡,这可能是百草枯的神经毒性作用机制之一。
OBJECTIVE: To investigate the manner and neurotoxic mechanism of paraquat-induced nigra cell death in mice. Methods: C57BL mice were treated with paraquat at different times, and the tyrosine hydroxylase (TH) immunohistochemistry and TUNEL method were used to detect the apoptosis of substantia nigra dopaminergic neurons by flow cytometry and transmission electron microscopy. Results: Immunohistochemical staining with TUNEL and double-stained TUNEL staining showed apoptosis-like changes of dopaminergic neurons in substantia nigra after 2 weeks of exposure to paraquat in C57BL mice. Flow cytometry analysis showed that after exposure to paraquat The number of apoptotic cells was the largest at 1 month, P <0.001 compared with the control group, but decreased at 2 months but still more than that of the control group (P <0.01). Conclusion: Exposure of paraquat to mice for a certain period of time can cause apoptosis of dopaminergic neurons in substantia nigra, which may be one of the mechanisms of neurotoxicity of paraquat.