锰的神经毒性机制探讨  

Study on manganese-induced neurotoxicity

作　　者：吴萍[1] 张杰[1] 李洁[2] 宣登峰[1] 赵峰[1] 褚金花[1] 李国君[1] 

机构地区：[1]首都医科大学环境与劳动卫生教研室,北京100054 [2]北京市丰台区疾病预防控制中心

出　　处：《中国公共卫生》2005年第7期800-802,共3页Chinese Journal of Public Health

基　　金：国家自然科学基金资助项目(30000140);教育部科学研究重点项目(00132);北京市科技新星计划(9558102800)

摘　　要：目的通过染毒人神经母细胞瘤细胞(SH-SY5Y)探讨锰致细胞的氧化损伤,为进一步研究锰的神经毒性机制提供科学依据。方法分别用0.00,0.25,0.50,0.75mmol/L的锰化合物染毒细胞24h,检测锰染毒的细胞中的抗氧化酶活力,包括超氧化物岐化酶(SOD)、谷胱苷肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)活力和抗氧化剂谷胱苷肽(GSH);用荧光分光光度计检测染锰细胞膜微粘度;用单细胞电泳检测细胞DNA链断裂情况;用0.50mmol/L锰染毒细胞24,48h,采用流式细胞仪检测细胞凋亡和细胞周期。结果锰染毒各组细胞抗氧化酶活力和抗氧化剂含量均有不同程度的降低,脂质过氧化产物丙二醛(MDA)有所升高;染锰细胞膜微粘度升高;锰染毒细胞各级彗星细胞数不同损伤程度增多,并与染锰浓度呈正相关;锰染毒24,48h的细胞,均出现明显的凋亡峰,细胞周期的分布也发生改变,S期细胞增多。结论锰可导致细胞处于氧化应激态和细胞损伤,这可能是锰的神经毒作用机制之一。Objective To find out the mechanism of manganese-induced neurotoxicity.The human dopamindrgic neuroblstoma cell SH-SY5Y was selected as test cell in the manganese cytotoxicity researches.Methods The cells were treated by 0.00,0.25,0.50 and 0.75?mmol/L Mn,respectively.24 hours later,the cellular super oxide dismutase(SOD),gulathione peroxidase (GSH-Px),catalase (CAT) and glutathione (GSH) were detected.The microviscosity of membrane was detected .The single cell gel electrophoresis was used to test the DNA strand breakage degree.After 0.50?mmol/L Mn treated cells 24?h and 48?h cell apoptosis and cell cycle were analyzed by flow cytometer.Results The activity of antioxidant enayme in Mn treated cells was lower than that of control group to some extent.The amount of MDA and the product of lipid peroxide in the treated cells were higher than those of control group The microviscosity of membrane of the treated cells was increased.DNA strand breakage degree demonstrated that the amount of comet cells was increased to some different extent in the treated cells.Moreover,there was positive correlation between the concentration of manganese and the damage degree.All Mn treated cells exhibited obvious apoptosis peaks,and the cell cycle was changed as well.The amount of S phase cells was increased.Conclusion Manganese could make the cells hold the oxidative stress status and could induce cells damage.It might be one of manganese-induced neurotoxicity mechanisms.

关 键 词：锰 氧化应激 细胞损伤 神经毒作用机制 

分 类 号：R994.6[医药卫生—毒理学]