丘脑底核深部脑刺激改善帕金森病模型大鼠自发跑轮行为的研究  

High-frequency stimulation of the subthalamic nucleus improves impaired voluntary wheel running behavior in hemiparkinsonian rats

作　　者：潘琪[1] 张旺明[2] 肖宗宇[3] 罗非[4] 徐如祥 

机构地区：[1]海南医学院附属医院神经外科,海口570102 [2]南方医科大学珠江医院神经外科 [3]青海大学附属医院神经外科 [4]北京中国科学院心理研究所 [5]陆军总医院附属八一脑科医院

出　　处：《立体定向和功能性神经外科杂志》2016年第4期193-198,共6页Chinese Journal of Stereotactic and Functional Neurosurgery

基　　金：国家自然科学基金项目(编号:30872662);海南医学院科研培育基金项目(编号:HY2015-19)

摘　　要：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 high-frequency lamic nucleus can improve impaired voluntary wheel running behavior stimulation of the subthain rats with unilateral 6- hydroxydopamine lesions. Methods Male Sprague-Dawley rats were assigned to 2 groups. 6- OHDA group （n=24） and control group （n=11）. A stimulation electrode was implanted into the right subthalamie nucleus. The unilateral 6-OHDA rat model was induced by injection of 6- OHDA into unilateral medial forebrain bundle. Voluntary wheel running activity and limb-use a- symmetry was assessed in successfully lesioned rats （n= 17） and control rats. HFS of the STN （130 Hz,pulse width 60 μs,50-175 μA） was delivered during behavioral tests. The lesioned degree of dopaminergic neurons in the substantia nigra was evaluated by immunohistochemistry staining of tyrosine hydroxylase. The location of the tip of the stimulating electrode was determined by hematoxylin and eosin staining. Results Seventeen out of the 24 rats were successfully lesioned after the injection of 6-OHDA into MFB. In the limb-use asymmetry test, the limb-use asymmetry score during STN-DBS decreased significantly （P= 0. 038） in successfully lesioned rats,compared with the score without STN-DBS. Compared with the score before lesion, the difference is not significant （P=0.07）. In the voluntary wheel running test,compared with the test without STN-DBS, In the voluntary wheel running test, compared with the test without STN-DBS,the values during STN-DBS increased in the number of running bouts （P=0. 032）, the distance moved in the wheel （P = 0. 03） and average peak speed in running bouts （P= 0. 035）, while the value of average duration from the running start to the peak speed decreased （P = 0.035）. Compared with the values before lesion, the differences are not significant. Conclusion High-frequency stimulation of the subthalamic nucleus improves impaired voluntary wheel running behavior in rats with unilateral 6-hydroxydopamine lesions. Voluntary wheel runn

关 键 词：帕金森病 丘脑底核 深部脑刺激 前肢使用不对称测试 跑轮行为测试 

分 类 号：R742.5[医药卫生—神经病学与精神病学]