The purpose of this study is to clarify that exercise may improve the motor dysfunction of Parkinson’s disease (PD) model rats by increasing the reuptake of glutamate (Glu) in the striatum. The neurotoxin 6-hydroxydopamine (6-OHDA) was injected into the medial forebrain bundle (MFB) of the rats’ right brain to establish PD model rats with unilateral injury, and the sham operation group was given the same dose of normal saline at the same site as the control group. The reliability of the model was evaluated by apomorphine (APO)-induced rotation test combined with tyrosine hydroxylase (TH) immunohistochemical staining in the substantia nigra and striatum. The exercise group started treadmill training intervention (11 m/min, 30 min/day, 5d/week, and 4 weeks in total) 1 week after the operation. The balance bar test, suspension test, and the tail-lifting handstand test were used to evaluate exercise performance of rats; RT-PCR and western blotting were used to detect protein and mRNA expression of glutamate transporter-1 (GLT-1) and glutamine synthetase (GS) in the striatum; and isotope labeling was used to detect the ability of Glu reuptake in the striatum. (1) Compared with PD group, the number of TH immunoreactive cells in the substantia nigra and the content of TH immunoreactive fibers in the striatum did not change significantly in PD + Ex group. (2) Compared with PD group, the latency and total time of crossing the balance beam were significantly shorter (P < 0.01), the retention time of two forepaws on the metal wire was significantly longer (P < 0.01), the maximum lifting of head and trunk was significantly increased (P < 0.01) in PD + Ex group. (3) Compared with PD group, the ability of Glu reuptake in the striatum was significantly increased (P < 0.05), the expression levels of GLT-1 and GS mRNA in the striatum were significantly increased (P < 0.05), the protein expression of GLT-1 and GS in the striatum was significantly upregulated (P < 0.05) in PD + Ex group. Exercise intervention can significantly improve the motor dysfunction of PD model rats, increase the ability of striatal Glu reuptake significantly, and upregulate the expression levels of GLT-1 and GS protein and GS mRNA significantly. Exercise intervention may increase the protein expression level of GLT-1 and increase the reuptake ability of Glu in the striatum, thereby reducing the excitotoxic effect of excessive Glu on the postsynaptic membrane, and ultimately alleviate the motor dysfunction in PD model rats.

本研究的目的是阐明运动可以通过增加纹状体中谷氨酸 (Glu) 的再摄取来改善帕金森病 (PD) 模型大鼠的运动功能障碍。将神经毒素6-羟基多巴胺（6-OHDA）注入大鼠右脑内侧前脑束（MFB），建立单侧损伤PD模型大鼠，假手术组给予等剂量生理盐水。与对照组相同的部位。通过阿扑吗啡（APO）诱导的旋转试验联合酪氨酸羟化酶（TH）免疫组化染色黑质和纹状体来评估模型的可靠性。运动组在术后1周开始跑步机训练干预（11 m/min、30 min/天、5 d/周，共4周）。平衡杆测试、悬挂测试、采用提尾倒立试验评价大鼠运动能力；RT-PCR和western blotting检测纹状体中谷氨酸转运蛋白1（GLT-1）和谷氨酰胺合成酶（GS）的蛋白和mRNA表达；同位素标记用于检测纹状体中Glu的再摄取能力。(1)与PD组相比，PD+Ex组黑质中TH免疫反应细胞数和纹状体中TH免疫反应纤维含量无明显变化。(2)与PD组相比，穿越平衡木的潜伏期和总时间明显缩短（RT-PCR和western blotting检测纹状体中谷氨酸转运蛋白1（GLT-1）和谷氨酰胺合成酶（GS）的蛋白和mRNA表达；同位素标记用于检测纹状体中Glu的再摄取能力。(1)与PD组相比，PD+Ex组黑质中TH免疫反应细胞数和纹状体中TH免疫反应纤维含量无明显变化。(2)与PD组相比，穿越平衡木的潜伏期和总时间明显缩短（RT-PCR和western blotting检测纹状体中谷氨酸转运蛋白1（GLT-1）和谷氨酰胺合成酶（GS）的蛋白和mRNA表达；同位素标记用于检测纹状体中Glu的再摄取能力。(1)与PD组相比，PD+Ex组黑质中TH免疫反应细胞数和纹状体中TH免疫反应纤维含量无明显变化。(2)与PD组相比，穿越平衡木的潜伏期和总时间明显缩短（P  <  0.01），PD+Ex组两只前爪在金属丝上的停留时间显着延长（P  <  0.01），头部和躯干的最大抬起显着增加（P  <  0.01）。(3)与PD组相比，纹状体中Glu重摄取能力显着增强( P  <  0.05 )，纹状体中GLT-1和GS mRNA的表达水平显着升高( P  < 0.05 )，蛋白表达水平显着升高( P <  0.05 )纹状体中 GLT-1 和 GS 的表达显着上调（P  <  0.05) 在 PD + Ex 组中。运动干预可显着改善PD模型大鼠的运动功能障碍，显着提高纹状体Glu再摄取能力，显着上调GLT-1、GS蛋白和GS mRNA的表达水平。运动干预可提高GLT-1蛋白表达水平，增加纹状体中Glu的再摄取能力，从而降低过量Glu对突触后膜的兴奋毒性作用，最终缓解PD模型大鼠的运动功能障碍。