帕金森病黑质多巴胺神经元的凋亡与其发病机制

目的研究帕金森病黑质多巴胺神经元的死亡机制.方法用四唑盐法及流式细胞仪观察囊泡单胺类转运体(Vesicular Monoamine Transporter,VMAT)功能抑制对大鼠嗜铬细胞瘤(pheochromocytoma cell,PC12)细胞凋亡的影响.结果多巴胺浓度为0.15,0.30,0.45,0.60 mmol/L时,PC12细胞生存率为(89.3±7.7)%,(62.9±4.3)%,(42.5±2.7)%,(37.6±3.7)%,与对照组100%比较0.30组差异有显著性意义(t=2.373～5.323,P＜0.05),0.45组与0.60组比较差异有显著性意义(t=4.673～5.323,P＜0.01),利血平协同多巴胺作用时,其生存率为(73.7±3.9)%,(49.8±2.1)%,(31.6±1.9)%,(20.1±1.7)%,与对照组100%比较,差异有显著性意义(t=3.043～5.673,P＜0.05).结论VMAT功能抑制引发了多巴胺的内源性毒性,进而诱发多巴胺神经元的凋亡,可较好解释帕金森病的发病机制.

Mechanisms for dopaminergic cell apoptosis in Parkinson's disease

AIM: To investigate the mechanisms responsible for cell death of dopaminergic neurons in Parkinson's disease(PD).METHODS: The inhibitory effect of vesicular monoamine transporter (VMAT) function on apoptosis of rat pheochromocytoma cells(PC12) was studied by using flow cytometric analysis.RESULTS: Survival rate of dopamine-treated PC12 cells was (89.3 + 7.7) %,(62.9 ± 4.3)%, (42. 5 + 2.7)%, (37.6 + 3.7)% when dopamine level was at 0. 15, 0. 30, 0. 45, and 0.60 mmol/L respectively. The 100% survive rate in control group P12 cells differed significantly from that in dopamine 0. 3 mmol/L group( t = 2. 373 - 5. 323, P ＜ 0.05), and differed significantly from that in dopamine 0. 45 and 0. 60 mmol/1 groups( t = 4. 673 - 5. 323, P ＜ 0.01 ) .With additional reserpine treatment, survive rate of dopamine-treated P12 cells reduced to(73.7 ±3.9)%, (49.8 +2. 1)%, (36. 1 ± 1.9)%, and(20. 1 +1.7)%. There was a significant difference in survive rate between control and experimental groups ( t = 3. 043 - 5. 673, P ＜ 0. 05).CONCLUSION: One of the potential underlying mechanisms for PD is the inhibition of VMAT function that leads to endotoxity of dopamine, thus induces apoptosis of dopaminergic neurons.