囊泡单胺转运体在脑组织中的分布特征与帕金森病相关性的研究

A study of relationships between distribution of vesicular monoamine transporter in brain and PD

目的探讨囊泡单胺转运体(VMAT2)在脑组织中的分布特征与帕金森病(PD)的关系。方法使用利血平、神经毒素1-甲基-4-苯基-四氢吡啶(MPTP)及联合利血平和MPTP分别造成C57BL小鼠的PD模型和分别收集不同胎龄自然流产的新鲜胎儿,应用免疫组织化学方法和Western blot观察VMAT2和酪胺酸羟化酶(TH)在黑质致密部、腹侧被盖和蓝斑分布的变化。结果免疫组织化学分析及Western blot显示,PD小鼠较对照组小鼠VMAT2和TH阳性神经元细胞数目在黑质致密部明显减少,腹侧被盖和蓝斑中的阳性神经元细胞数无明显变化;同时发现在小鼠正常对照组和人胎脑中VMAT2在黑质致密部中的分布既少于腹侧被盖也少于蓝斑。结论这种对多巴胺神经元具有保护作用的VMAT2在黑质致密部中的分布少于腹侧被盖和蓝斑,黑质致密部保护作用薄弱是PD黑质选择性受损的重要原因。

Objective To investigate the distribution of vesicular monoamine transporter（VMAT2） in brain and their relationships with Parkinson disease（PD）. Methods PD model of C57BL mice induced by reserpine, MPTP, reserpine plus MPTP was used respectively and human embryonic brains of different parts （substantia nigrapars compacta,SNC）, ventral tegmental areas（VTA） and locus coeruleus （LC） were examined by immunohistochemistrical staining and Western blot. Results The number of VMAT2- positive neurons and the number of TH- positive neurons in SNC were significantly reduced in PD model than the control, but there was no great difference in VTA and LC between PD model and the control. The distribution of VMAT2 in the control and human embryonic brains in SNC was less than that in both VTA and LC. Conclusion The amount of VMAT2 that has protective effect on the DA neurons in SNC is less than that in both VTA and LC. The weakage of the protecting function of VMAT2 in SNC may be the important cause of the selective DA neurons loss.