早期损毁丘脑底核可阻止6-OHDA对大鼠多巴胺能神经元的损伤作用

Prevention of neurotoxin damage of 6-OHDA to dopaminergic nigral neuron by early subthalamic nucleus lesions

目的 :观察不同时期毁损丘脑底核 (STN)对大鼠中脑黑质多巴胺 (DA)神经元 6 -羟基多巴胺 (6 OH DA)损伤的保护作用。方法 :将 6 0只Wistar大鼠随机分为 6组 ,每组 10只。对照组采用 6 -OHDA立体定向注入大鼠右侧前脑内侧束 (MFB)和中脑被盖腹侧区 (VTA) ,制成偏侧帕金森病 (PD)模型。实验组分为第Ⅰ、Ⅱ、Ⅲ、Ⅳ和Ⅴ组 ,分别于 6 OHDA注射前 7d、注射后 1h、2h、3d、7d5个不同时间点 ,局部注射海人藻酸 (KA)破坏STN。 4周后处死大鼠 ,采用免疫组化染色方法 ,定量测量各组大鼠黑质致密区 (SNc)区TH免疫阳性反应神经元数目。实验数据采用方差分析和t检验统计学处理。结果 :第Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ实验组以及对照组的注射侧TH神经元存活数目分别为 71.46± 6 .84、5 7.0 7± 5 .5 4、5 1.0 9± 4.85、12 .6 8± 2 .6 7、4.15± 1.6 0和 3.40± 1.5 4个 /每张切片 ,为对侧的 96 .7%、72 .9%、6 9.8%、17.2 %、5 .6 %及 4.4%。各实验组注射侧TH神经元均比对照组同侧数目多 (P <0 .0 1、0 .0 5 ) ,但V组无显著性差异 (P >0 .0 5 )。各组实验组之间比较 ,均有明显差异 ,其中以Ⅰ组TH神经元存活的数量最多 (P <0 .0 1)。结论 :早期毁损STN ,可减轻 6 -OHDA对SNc区DA能神经元的损伤和细胞数量的缺失 ,晚期毁损对?

Objective:To investigate the possibility that subthalamic nucleus (STN) ablation could prevent the toxicity of the selective dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA).Methods:Sixty rats in were divided into 6 groups (n=10).Control group received a unilateral microinjection of 6 OHDA into the right ventral tegmental area (VTA) and the right median forebrain bundle(MFB).Group 1 received an administraiton of kainic acid (KA) into the right STN and 1-week later an injection of 6-OHDA in the right VTA and MFB.Group 2,3,4,5 received an injection of 6-OHDA in the right VTA ans MFB,1h,2h,3d,and 7d before KA in the right STN respectively.Four weeks later, the changes of tyrosine hydroxylase (TH)-positive(dopaminergic) neurons in the SNc were investigated with immunocytochemical and morphometrical methods.Results: The number of TH positive cells in the SNc on the injected side of treated groups (group 1,2,3,4 and 5)and control group were 71.46±6.84,57.07±5.54,51.09±4.85,12.68±2.67,4.15±1.60 and 3.40±1.54/slice, which decreased to 96.7%,72.9%,69.8%,17.2%,5.6%and 4.4% of the non-injected side,respectively.The number of TH positive in group 1,2,3 and 4 significantly increase in comparison with the controls ( P <0.05,0.01).In group 5,there were no remarkable difference in contrast to the number of TH positive neurons of the controls( P >0.05).The difference of the number of TH positive between group 1,2,3,4,and 5 were statistically significant( P <0.01).Conclusion:The results indicate that early STN ablation can provide antiglutamate-based neuroprotection of the dopaminergic nigrostriatal pathway against 6-OHDA toxicity.