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为了制作Huntington病(Huntington disease,HD)兴奋性动物模型,本文向大鼠纹状体内注射喹啉酸(quinolinic acid,QA),并观察了其行为学改变和纹状体内GABA能神经元数目的改变。采用立体定向手术向大鼠单侧纹状体内注入1μl240nmol/μl喹啉酸制作动物模型。手术后2周通过腹腔注射阿朴吗啡、旷场试验(open-field test)、Morris水迷宫实验观察和比较模型组大鼠与对照组大鼠的旋转行为、对新环境的探索行为、学习记忆能力的差异,并用免疫组化方法观察了纹状体钙结合蛋白Calbindin阳性细胞数的变化。结果显示:模型组大鼠经阿朴吗啡诱导出现转向损伤侧的旋转行为;旷场分析中模型鼠跨格次数、后腿站立次数及理毛次数减少(P<0.05),说明其对新环境的探索行为和适应能力下降;Morris水迷宫实验表明模型大鼠逃避潜伏期延长(P<0.05)、运动速度减慢(P<0.05)、对原平台所在象限记忆频度减低(P<0.05),说明模型大鼠学习记忆能力下降,空间参考记忆缺陷;免疫组化实验显示模型大鼠纹状体内钙结合蛋白Calbindin阳性细胞数减少。上述结果表明利用立体定向技术向大鼠单侧纹状体注射QA建立的HD动物模型可以表现出与HD相似的行为学和组织病理学改变,是一种可靠的HD兴奋性毒性模型。
In order to make a Huntington disease (HD) excitatory animal model, we injected quinolinic acid (QA) into the striatum of rats and observed its behavioral changes and the number of GABAergic neurons in the striatum change. Animals were injected with 1μl 240nmol / μl quinoline acid into the unilateral striatum by stereotactic surgery. Two weeks after the operation, apomorphine, open-field test and Morris water maze test were used to observe and compare the rotation behavior of rats in the model group and the control group, exploration behavior in new environment, learning and memory Ability of the difference, and using immunohistochemistry method to observe the changes of striatal calcium-binding protein Calbindin positive cells. The results showed that the rotation behavior of rats in the model group induced by apomorphine turned to injury side. In the open field analysis, the number of traversing grids, the number of standing hind legs and the number of grooming decreased (P <0.05) (P <0.05), the speed of motion slowed down (P <0.05), and the memory frequency of the quadrant where the original platform was located decreased (P <0.05) The results showed that the learning and memory abilities of the model rats decreased and the space reference memory deficits. The number of Calbindin-positive cells in the striatum of the striatum was decreased by immunohistochemistry. The above results indicate that HD animal model established by injecting QA to unilateral striatum using stereotactic technique can show similar behavioral and histopathological changes as HD and is a reliable model of HD excitotoxicity.