6-OHDA诱导帕金森病大鼠模型行为学及脑内神经递质的动态变化

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目的:观察6-羟基多巴胺(6-OHDA)诱导帕金森病大鼠模型(PD)不同时间点行为学及左侧纹状体内多巴胺(DA)和乙酰胆碱(Ach)含量的变化。方法:采用6-OHDA左侧纹状体两点注射法建立PD大鼠模型,观察术后不同时间点大鼠经阿扑吗啡(APO)诱导出现旋转行为改变,ELISA法测定各时间点大鼠左侧纹状体区DA和Ach含量,HE染色观察左侧中脑黑质区多巴胺能神经细胞的病理形态学改变。结果:行为学方面:假手术组各时间点大鼠经APO诱导无旋转行为;6-OHDA组大鼠经APO诱导出现异常旋转行为,48 h后右侧旋转速度逐渐增快,4周右侧旋转速度达到高峰,4周到8周恒定右侧旋转速度稳定。DA和Ach含量变化:假手术组各时间点DA和Ach无明显变化。6-OHDA组造模术后6h,DA含量降低,术后1周、2周、4周DA含量明显减少,术后4周与8周DA含量比较无明显差异。HE染色:假手术组各时间点左侧黑质区神经元细胞形态正常。6-OHDA组6 h少量神经细胞肿胀,24 h、48 h、1周可见大量神经细胞肿胀,部分核裂变,胶质细胞增多,2 w时神经细胞肿胀减轻,核仁明显偏移或破裂,神经元数量减少,4周、8周神经细胞凝固性坏死,伴有大量胶质细胞弥漫性或局限性增生。结论:6-OHDA组造模后,随着造模时间延长,大鼠左侧纹状体内DA含量逐渐下降,Ach含量逐渐上升,于术后4周达到稳定状态,与大鼠右侧旋转行为表现一致;HE染色见左侧纹状体神经元随时间延长表现为变性、坏死,胶质细胞增生。 OBJECTIVE: To observe the changes of behavior and contents of dopamine (DA) and acetylcholine (Ach) in left striatum of rats with Parkinson’s disease (PD) induced by 6-hydroxydopamine (6-OHDA) Methods: PD rats were established by injection of 6-OHDA in the left striatum. PD rats were induced by apomorphine (APO) at different time points after operation. The rats in each time point The contents of DA and Ach in the left striatum and the histopathological changes of dopaminergic neurons in the left substantia nigra region were observed by HE staining. RESULTS: In behavioral aspects, rats in the sham-operated group were induced to rotate without APO at all time points. In the 6-OHDA group, abnormal rotation was induced by APO, and the right rotation speed gradually increased after 48 h. Rotation speed reached its peak, 4 weeks to 8 weeks constant rotation speed of the right side of the stable. DA and Ach content changes: Sham operation group at each time point DA and Ach no significant change. After 6 h, the content of DA in 6-OHDA group decreased, and the content of DA in 1 week, 2 weeks and 4 weeks after operation decreased significantly. There was no significant difference in DA content between 4 weeks and 8 weeks after operation. HE staining: the sham group at each time point left substantia nigra neurons normal morphology. 6-OHDA group a small amount of nerve cell swelling 6 h, a large number of 24 h, 48 h, 1 week can be seen a large number of nerve cell swelling, some nuclear fission, glial cells increased, 2 w when the nerve cell swelling reduced significantly offset or rupture of nucleoli, Decreased number of neurons, 4 weeks, 8 weeks of nerve cell coagulation necrosis, accompanied by a large number of glial diffuse or limited proliferation. CONCLUSION: After 6-OHDA group is established, the content of DA in the left striatum gradually decreases and the content of Ach gradually increases with the prolongation of modeling time, and reaches steady state at 4 weeks after the operation, Consistent performance; HE staining showed that the left striatum neurons showed degeneration, necrosis, glial proliferation over time.
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