摘要： 目的 比较6-羟基多巴胺损毁单侧内侧前脑束（MFB）和单侧纹状体的帕金森病大鼠模型在不同时期行为学的差异。方法 将62只成年雄性SD大鼠随机分为4组：1位点纹状体损毁模型组（n=18）、4位点纹状体损毁模型组（n=18）、MFB损毁模型组（n=18）和假手术组（n=8）。通过甲基苯丙胺诱导的旋转实验、溴隐亭诱导的旋转实验和步行实验比较损伤后早期（4周后）和晚期（6个月后）大鼠行为学的变化，并通过免疫组织化学和结合分析实验计算病灶侧阳性多巴胺神经元脱失率和多巴胺转运蛋白、D2受体结合率。结果 甲基苯丙胺诱发1位点纹状体损毁模型组、4位点纹状体损毁模型组和MFB损毁模型组大鼠均产生朝向病灶同侧的旋转；溴隐亭诱发纹状体损毁模型产生朝向病灶同侧的旋转，而MFB损毁模型组则产生朝向病灶对侧的旋转。成模早期和晚期不同模型组组间比较以及同一模型组中成模早期和晚期比较，旋转圈数的差异均无统计学意义。步行实验结果显示，同一模型组中，成模早期和晚期病侧肢体运动启动时间明显长于健侧肢体（P < 0.001），病侧肢体步长长度明显短于健侧肢体（P < 0.001），病侧肢体前后步伐调整数明显少于健侧肢体（P < 0.001）；同一模型组中，病侧肢体成模早期与晚期、健侧肢体成模早期与晚期比较，上述结果均无统计学差异。而多巴胺神经元脱失率、多巴胺转运蛋白及D2受体结合率在不同时期的3种模型病变侧呈现出与行为学实验结果不一致的动态变化过程。结论 帕金森病大鼠模型的行为学活动并非仅由某些单一多巴胺能参数决定，而是由整个多巴胺能系统的综合效应控制。

6-羟基多巴胺损毁单侧内侧前脑束和单侧纹状体的帕金森病大鼠模型早期和晚期行为学

孙炜¹, 吴春明¹, 刘张², 难波宏树³

1. 大连医科大学附属第一医院神经外科, 辽宁 大连 116011;
2. 大连医科大学附属第一医院儿科, 辽宁 大连 116011;
3. 日本滨松医科大学附属医院神经外科, 静冈 滨松 431-3192

收稿日期:2022-10-10出版日期:2023-02-28发布日期:2023-02-04
通讯作者:刘张E-mail:liuzhang060312@163.com
作者简介:孙炜(1979-),男,副教授,博士.
基金资助:辽宁省自然科学基金（2019-ZD-0639）；大连市科技创新基金（2019J13SN104）


关键词: 帕金森病, 行为学实验, 多巴胺能系统, 大鼠模型
Abstract: Objective To compare the behavioral differences at different stages after unilateral striatal and medial forebrain bundle (MFB) lesions induced by 6-hydroxydopamine in a rat model of Parkinson disease. Methods Sixty-two adult male Sprague-Dawley rats were randomly divided into one-lesion striatal model group (n=18), four-lesion striatal model group (n=18), MFB lesioned model group (n=18), and a sham operated group (n=8). We compared the behavioral differences in rotational movements induced by using methamphetamine/bromocriptine and stepping test at early (4 weeks after lesion) and later stages (6 months after lesion). The loss rate of dopamine neurons and binding rate of dopamine transporters and D2 receptors were calculated using immunohistochemistry and binding assay. Results Ipsilateral rotations to the lesion side were caused by methamphetamine in one- and four-lesion striatal and MFB models. Ipsilateral rotations to the lesion side were caused by bromocriptine in one- and four-lesion striatal models but contralateral rotations to the lesion side in the MFB model. No significant difference in the number of rotations was noted between different model groups at the early and late stages of modeling, and between the early and late stages of modeling in the same model. The results of stepping test showed that, compared with the normal side, the initiation time was significantly longer (P < 0.001), stepping length was significantly shorter (P < 0.001), and adjusting steps was significantly less on the lesion side (P < 0.001) in the same model. No statistical difference was noted on the lesion limb and normal limb in the same model at early and later stages. However, the loss rate of dopamine neurons and binding rate of dopamine transporters and D2 receptors on the lesion side of the three models at different stages showed dynamic changes inconsistent with the results of behavioral test. Conclusion Our results suggest that behavioral characteristics might be controlled by comprehensive effects of the whole dopaminergic system, instead of variation in a few parameters of the dopaminergic system.
Key words: Parkinson disease, behavioral test, dopaminergic system, rat model
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