左旋多巴诱导PC12细胞凋亡及谷胱甘肽对细胞的保护作用

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。

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

AIM:To study the induction of apoptosis of pheochromocytoma (PC12) cell by L - dopa and the clinical significance. METHODS: Using PC12 cells as the medel of dopaminergic neurons,in addition to electron microscopy, agarose gel electrophoresis and flow cytometry, the apoptosis ratio by L - dopa and the effect of antioxi- dant glutathione on PC12 cells were observed. RESULTS: Treabent of PC12 cells with L - dopa in concentrations of 50 μmol/L, 100μmol/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 cobant with fragment pragment propartions of agarose gel electrophoresis, mere 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 treat- ment of L - dopa.