1-甲基-4-苯基-吡啶盐致多巴胺能细胞系MES23.5的死亡机制  

The Mechanism of 1-methyl-4-phenyl-pyridinium Resulting in the Death of Dopaminergic Cell Line MES23.5

作　　者：傅求真[1,2] 徐胜利[1] 左晓虹[1] 徐燕玲[1] 陈彪[1] 

机构地区：[1]首都医科大学宣武医院北京老年病医疗研究中心 [2]第四军医大学唐都医院神经内科,西安710038

出　　处：《细胞生物学杂志》2004年第5期539-543,共5页Chinese Journal of Cell Biology

基　　金：国家重点基础研究发展规划项目(973计划)(No.G2000057005)国家自然科学基金(No.30371574)资助项目~~

摘　　要：通过测定环境毒素1-甲基-4-苯基-吡啶盐(MPP+)作用于多巴胺能细胞系MES23.5后细胞存活率的变化及细胞线粒体膜电位(△ΨM)、活性氧(ROS)、羟自由基、超氧化物岐化酶(SOD)的变化,发现MPP+作用于多巴胺能细胞系MES23.5,可导致细胞存活率显著性减少,浓度达到200mol／L以上后,细胞存活率的下降呈时间与MPP+浓度依赖;以200μmol／LMPP+作用细胞6-48h后,△ΨM逐渐下降、ROS、羟自由基逐渐增加,48h后SOD开始显著性减少。结果表明早期线粒体能量代谢障碍和膜电位变化导致ROS(尤其是羟自由基)含量增加是MPP+导致多巴胺能细胞氧化应激的原因,而细胞内自由基的清除机制受损,则最终导致细胞变性死亡。Through the measurement of the cellular viability, mitochondrial membrane potential reactive oxidant species (ROS) content, -OH and superoxide dismutase (SOD) content after the exposure of 1-methyl-4-phenyl-pyridinium (MPP+), the environment toxin, on dopaminergic cell line MES23.5, it was found that the cellular viability was significantly decreased after the exposure of MPP+ and the decrease was concentration and time dependent under more than 200 μmol/L MPP+. Significantly, the ΔΨM began to reduce and the ROS, the ·OH content began to increase gradually since 6 to 48 hours exposure of 200 μmol/L MPP+. The SOD content was not significantly reduced until 48 hours exposure. The results suggest that the increased ROS, especially ·OH, caused by disturbance of mitochondrial energy metabolism and the ΔΨM changes in early stage may result in MPP+-induced oxidative stress in dopaminergic cells and the damage of cellular free radical cleaning system may induce the dopaminergic cells degeneration and finally death.

关 键 词：1-甲基-4-苯基-吡啶盐 巴胺能细胞系 氧化应激 帕金森氏病 毒性作用 

分 类 号：Q25[生物学—细胞生物学]