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左旋多巴诱导PC12细胞凋亡及谷胱甘肽对细胞的保护作用

韩燕 陈俊抛 王洛伟 杨玉庆  陈沛源

  [摘 要] 目的:研究左旋多巴(L-dopa)对大鼠肾上腺髓质嗜铬细胞瘤(PC12)细胞的凋亡诱导作用并探讨其临床意义。方法:以PC12细胞为多巴胺(DA)神经元的细胞模型,利用电镜、DNA凝胶电泳结合图象分析仪、流式细胞术(FCM)等技术检测不同浓度L-dopa所致的凋亡率以及抗氧化剂谷胱甘肽(GSH)对它的影响。结果:流式术测得50 μmol/L、100 μmol/L、150 μmol/L处理组凋亡率分别为12.4%、24.4%、37.2%,与琼脂糖电泳的片断化DNA比例基本一致,与对照组(2.3%)有显著差异(P<0.01),L-dopa与GSH合用组凋亡率2.5%与对照组比较无显著差异(P>0.05)。结论:GSH可以阻断L-dopa 对PC12细胞的凋亡诱导作用,提示L-dopa 可能是通过氧化损害介导DA神经元凋亡,导致疗效减退。
  [主题词] 左旋多巴;细胞系;谷胱甘肽;PC l2细胞
  [中图分类号] Q279   [文献标识码] A
  [文章编号] 1000-4718(2000)05-0462-04

L-dopa induction of pheochromocytoma12 cells apoptosis and the protective function of glutathione

HAN Yan, CHEN Jun-pao, WANG Luo-wei, YANG Yu-qing, CHEN Pei-yuan
(Department of Neurology, The 456th Hospital of PLA, Jinan 250031, China)

  [Abstract] AIM:To study the induction of apoptosis of pheochromocytoma (PC12) cell by L-dopa and the clinical significance. METHODS:Using PC12 cells as the model of dopaminergic neurons, in addition to electron microscopy, agarose gel electrophoresis and flow cytometry, the apoptosis ratio by L-dopa and the effect of antioxidant glutathione on PC12 cells were observed.RESULTS:Treatment of PC12 cells with L-dopa in concentrations of 50 μmol/L,100 μmol/L and 150 μmol/L respectively for 24 hours, results revealed that the apoptosis ratio was 12.8%, 24.4%, 37.2%, respectively, which is in cordant with fragment propartions of agarose gel electrophoresis, more higher than that of control(2.3%)(P<0.01).The apoptosis ratio of glutathione+L-dopa group was similar to that of control(P>0.05). CONCLUTION:Induction of apoptosis by L-dopa could be inhibited by glutathione, and oxidative damage may be involved in the pathophysiology of dopaminergic neurons death after long-term treatment of L-dopa.
  [MeSH] Levodopa; Cell line; Glutathione;PC12 cells

  左旋多巴(L-dopa)及其复方制剂是治疗帕金森病(Parkinsom's disease, PD)最常用且最有效缓解症状的药物,但其疗效一般在2~4年后就会逐渐减退。L-dopa

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