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目的探讨丘脑底核(subthalamic nucleus,STN)深部脑刺激(deep brain stimulation,DBS)能否改善6-羟基多巴胺偏侧帕金森病模型大鼠自发跑轮行为。方法将35只Sprague-Dawley(SD)大鼠随机分为实验组24只和对照组11只。利用立体定向的方法将刺激电极埋入右侧丘脑底核。实验组大鼠右侧内侧前脑束内注射12μg 6-OHDA,对照组注射相同体积的生理盐水。对造模前、造模后和给予电刺激时的大鼠进行前肢使用不对称测试和自发跑轮行为测试。酪氨酸羟化酶免疫组化染色检测黑质多巴胺能神经元毁损程度。苏木素-伊红染色确定刺激电极尖端位置。结果从24只大鼠中获得了17只成功的PD大鼠模型。前肢使用不对称测试:与毁损后未给予STN-DBS时比较,电极尖端位于STN内的成功模型大鼠给予STN-DBS后,不对称指数显著下降(P=0.038),而与毁损前相比,差异不显著(P=0.07)。跑轮行为测试:与毁损后未给予STN-DBS时比较,电极尖端位于STN内的成功模型大鼠给予STN-DBS后,跑动次数(P=0.032)、跑动距离(P=0.03)和平均峰速度均(P=0.035)显著增加,而从跑动开始到峰速度的平均时间显著减小(P=0.001)。这些指标与毁损前比较,差异均无统计学意义。结论丘脑底核深部脑刺激能够改善6-羟基多巴胺偏侧帕金森病模型大鼠的自发跑轮行为,自发跑轮行为测试在一定程度上可用于筛选抗帕金森病药物或其他治疗方法。
Objective To investigate whether deep brain stimulation (DBS) of subthalamic nucleus (STN) can improve the spontaneous runner behavior in rats with 6-hydroxydopamine-induced Parkinson’s disease. Methods Thirty-five Sprague-Dawley rats were randomly divided into experimental group (n = 24) and control group (n = 11). Stimulation electrodes were buried in the right subthalamic nucleus using stereotactic methods. In the experimental group, 12μg of 6-OHDA was injected into the right medial forebrain and the control group was injected with the same volume of saline. The rats in the pre-model, model-group and model group were subjected to asymmetric forelimb test and spontaneous run-of-the-week behavioral test. Tyrosine hydroxylase immunohistochemical staining to detect the degree of nigral dopaminergic neuron damage. Hematoxylin-eosin staining determines the location of the tip of the stimulation electrode. Results Seventeen successful PD rat models were obtained from 24 rats. Asymmetric test of forelimb use: The asymmetry index was significantly decreased (P = 0.038) in the successful model rats with the most advanced electrodes in the STN compared with those without STN-DBS after the lesion, compared with those before the lesion , The difference was not significant (P = 0.07). Run-round behavioral test: The number of runs (P = 0.032), distance traveled (P = 0.03) and STN-DBS were significantly higher in STN-DBS-treated rats than in STN- The average peak velocity (P = 0.035) increased significantly, while the average time from the start of the treadmill to the peak velocity decreased significantly (P = 0.001). These indicators and damage before comparison, the difference was not statistically significant. Conclusion Deep brain stimulation of the subthalamic nucleus can improve the spontaneous running behavior of rats with 6-hydroxydopamine-induced Parkinson’s disease. The spontaneous run-of-the-mill behavior test may be used to screen anti-Parkinson’s disease drugs or other treatments.