6-羟基多巴诱发偏侧帕金森病样大鼠模型的制作和特征

The character of a 6-hydroxydopamine induced Parkinson's disease rat model

  • 摘要: 目的:了解6-OHDA注入大鼠一侧中脑黑质区所导致的行为、生化和组织学改变及该种帕金森病样大鼠模型的可靠性和稳定性。方法:采用雌性SD大鼠,在脑立体定位技术下,将6-OHDA注入大鼠右侧中脑黑质区,以损毁黑质多巴胺能细胞。用小动脉旋转行为监测仪记录Apomorphine诱发的大鼠异常旋转行为、脑组织液生化和组织形态的变化。结果:发现6-OHDA注入大鼠右侧中脑黑质后,大鼠向损毁对侧的旋转次数明显增加(大于280圈/40min),PD模型成功率为50.5%。PD鼠损毁侧脑组织液中多巴胺代谢产物DOPAC和HVA明显低于未损毁侧(P<0.05)。PD阳性鼠右侧黑质致密斑和腹侧背盖区处TH阳性细胞消失;而PD阴性鼠右侧仍部分存在。连续观察十个月PD样模型大鼠的异常旋转行为无自发性恢复。结论:6-OHDA可损毁黑质多巴胺能细胞,造成与帕金森患者相似的基本病理变化,是一种可靠而稳定的PD样大鼠模型

     

    Abstract: Objective: To evaluate the character of a 6 hydroxydopamine induced (6-OHDA) Parkinsonian (PD) rat model.Methods: Unilateral destruction of the dopaminergic neurons of substantia nigra were produced by stereotaxic injections of 6-OHDA in 128 female Sprague Dawley rats. The rats were tested for rotational behavior induced by apomorphine for 40 min every week. The rats demonstrating an average of at least 280 complete contralateral turns/40 min for 4 times in response to apomorphine were selected as PD rats. After 1 month of the lesions the extracelluar liquid were dialysed bilaterally by the intracerebral microdialysis technique. The levels of catecholamines and its metabolite were measured by high performance liquid chromatography analysis. Coronal sections through midbrain of the rat were stained for tyrosine hydroxylase immunohistochemistry. Results: A total 50.5% of the rats rotated over 280 turns per 40 min after 6-OHDA lesions. The PD rats didn't spontaniously occur recovery for 10 months. The levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), seretonin (5-HT), 5-hydroxyindoleacetic acid (5 HIAA) and adrenaline (AD) in lesioned side of the striatium were significantly reduced. TH immunohistchemistry of the midbrain sections revealed a nearly complete absence of TH-immunoreactive cells in the right substantia nigra pars compacta (SNC) and ventral tegmental area (VTA) for the PD rats. There were some TH-immunoreactive cells in the right substantia nigra pars compacta (SNC) and ventral tegmental area (VTA) for the PD rats. There were some TH-immunoreactive cells in the right SNC and VTA of the rats which rotated less 280 contralateral turns.Conclusion: The rats with 6-OHDA destruction of the neurons of substantia nigra may produce a similar neuropathological and biochemical changes to idiopathic Parkinson's disease. This is a stable Parkinsonian rat model.

     

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