【摘要】 目的:研究囊泡单胺类转运体(VMAT)功能抑制在帕金森病发病机制中的作用途径。方法:用MTT法及流式细胞仪观察VMAT功能抑制对大鼠嗜铬瘤细胞(PC12)存活的影响和细胞死亡方式。结果:单独作用的VMAT抑制剂利血平对PC12细胞无毒性作用;超过一定浓度的多巴胺(0.2mmol/L)对PC12细胞有毒性作用;利血平协同多巴胺明显增加多巴胺的毒性,使同样浓度的多巴胺诱发PC12细胞的凋亡率明显增加。随着多巴胺浓度的增加脂质过氧化物丙二醛(MDA)亦相应增加。受药物毒性作用的PC12细胞主要以凋亡途径死亡。结论:VMAT功能抑制触发的多巴胺内源性毒性可能通过氧化应激诱发凋亡和坏死而发挥毒性作用。更多还原

【Abstract】 Objective: To study the effecting pathway of VMATs inhibition in the pathogenesis of Parkinson disease. Meathods:To observe the effect of inhibit ion of VMAT on PC12 cells and their death way with MTT and flow cytometer. Resul ts: Reserpine,the inhibitor of VMAT,itself had no poisonous effect on PC12 cells . Dopamine had poisonous effect on PC12 cells when its concentration was over a definite level (0.2 mmol/L).Reserpine’s cooperation with dopamine obviously incr eased the poisonous effect of dopamine and the apoptosis ratio of PC12 cells ind uced by the same concentration of dopamine was obviously increased. The quantity of MDA in cytoplasm increased with the increment of dopamine concentration. The PC12 cells dealed with medicine went to death mainly with the way of apoptosis. Conclusion: The endogenous toxin triggered by the inhibition of VMAT may carry on its effection through oxidative stress inducing apoptosis and necrosis.更多还原