热休克蛋白70在大鼠黑质多巴胺神经元损伤中的表达

Experimental Study on the Expression of Heat Shock Protein in the Injured Dopaminergic Neurons

目的 :探讨热休克蛋白 70 (HSP70 )在大鼠黑质多巴胺 (DA)神经元损伤中的表达以及在帕金森病 (PD)诊断中的意义。方法 :将 48只大鼠随机分为黑质DA神经元损毁组 (PD组 )和对照组各 2 4只。PD组注射 6 羟多巴胺 (6 OHDA)损毁大鼠黑质DA神经元 ,对照组仅注射 6 OHDA溶媒。于注射后 1、7、14及 2 1d采用免疫组织化学、尼氏染色、电镜手段动态观察HSP70在损毁的DA神经元中的表达以及DA神经元形态学变化。结果 :在 6 O HDA损毁黑质 1～ 2 1d ,对照组黑质HSP70表达和尼氏细胞计数差异无显著性 (P >0 .0 5 )。PD组HSP70表达在 1d最高 ,7d锐减 ,14和 2 1d则逐渐减少 ,分别为 2 5 %、74%、87%及 88% ;尼氏细胞计数在 4个时间点分别减少1%、13%、35 %及 48% ;超微结构损伤程度呈进行性加重。结论 :PD渐进性发病具有其形态学基础 ,HSP70可作为DA神经元存活的指标和早期诊断PD的指标。

Objective:To observe the expression of heat shock protein 70 (HSP70) in the dopaminergic (DA) neurons ruined by 6-hydroxydopamine and the morphological changes in dopaminergic neurons. Methods:48 rats were randomly divided into a group of DA nuerons in nusubstantia nigra (PD group, n=24) ruined by injection of 6-hydroxydopamine and control group (n=24) only injected with the media for 6-hydroxydopamine. On the 1st, 7th, 14th and 21st day after injection, by using immunohistochemistry, Nissl's staining method, electromicroscopy, the expression of HSP in the ruined DA neurons was detected and the morphological changes of DA neurons were observed. Results:On the 1st to 21st day after injury, the expression of HSP and Nissl's staining positive cells showed no significant difference between PD group and control group. In the PD group, the expression of HSP70 reached the peak on the 1st day, sharply decreased on the 1st day to the 7th day, then decreased gradually from the 14th to the 21st day, 25 %, 74 %, 87 % and 88 % respectively. Nissl's staining positive cells at the 4 time points were decreased by 1 %, 13 %, 35 % and 48 % respectively. The ultrastructual lesions were progressively worsened. Conclusion:Progressive development of Parkinson's disease has its basis of morphology. HSP70 can be used as a marker for detecting stock of DA neurons and early diagnosis of PD.