Abstract: Objective Investigate the effect of treadmill exercise on the degeneration of dopaminergic neurons in substantia nigra and motor impairments in a rat model of Parkinson's disease. Methods Orty male SD rats were randomly divided into model group,model + treadmill exercise group,green fluorescent protein group and green fluorescent protein + treadmill exercise group,with 10 rats in each group.The first two groups of rats were injected with rAAV-CMV-hSNCA.The latter two groups of rats were injected with rAAV-CMV-GFP.Rats given treadmill exercise began treadmill exercise 7 days after operation for 12 weeks.Rats without exercise were also placed on the treadmill,but did not exercise.Open field test,forelimb asymmetry test and apomorphine induced rotation test were used to evaluate the motor behavior of rats.Immunofluorescence staining was used to investigate the expression of α-synuclein in tyrosine hydroxylase immunoreactive neurons of substantia nigra.The number of tyrosine hydroxylase immunoreactive neurons in substantia nigra was detected by immunohistochemical staining. Results Parse tyrosine hydroxylase immunoreactive neurons could be seen in the rightsubstantia nigra of the model group,and a large number ofα-synuclein were expressed in the neurons.The aggregationsof α-synuclein were detected insome neurons.Compared with the model group,the survival rate of tyrosine hydroxylase immunoreactive neurons in the substantia nigra of the model+treadmill exercise group was significantly higher (P=0.000).In the open field experiment,compared with the model group,the shuttle distance (P=0.001),the number of lower limb standing (P=0.031) and the total running time (P=0.007) of the model+treadmill exercise group were significantly increased.In the forelimb asymmetry test,compared with the model group,the asymmetry index of the model+treadmill exercise group decreased significantly (P=0.000).In the apomorphine induced rotation experiment,compared with the model group,the number of rotation circles of the model+treadmill exercise group was significantly reduced (P=0.017). Conclusion Treadmill exerciseimprovesthe degeneration of dopaminergic neurons in substantia nigra and motor impairments in a transgenic rat model of Parkinson's diseasewith overexpression of α-synuclein.

Key words: Parkinson's disease, Treadmill exercise, Alpha-synuclein, Dopaminergic neuron, Rats

摘要： 目的 探讨跑台运动对帕金森病大鼠模型的黑质多巴胺能神经元退变和运动障碍表现的影响。方法 40只雄性SD大鼠,随机分为模型组、模型+跑台训练组、绿色荧光蛋白组和绿色荧光蛋白+跑台训练组,每组10只大鼠。前两组大鼠右侧黑质内注射人野生型α-突触核蛋白重组腺相关病毒,后两组大鼠右侧黑质内注射绿色荧光蛋白重组腺相关病毒。给予跑台训练的大鼠在手术后7天开始进行跑台训练,持续12周。不进行训练的大鼠同样置于跑台内,但不进行跑台运动。采用旷场实验、前肢使用不对称测试和阿扑吗啡诱导旋转实验评价大鼠的运动行为。采用免疫荧光染色检测α-突触核蛋白在黑质内酪氨酸羟化酶免疫阳性神经元内的表达。采用免疫组化染色检测黑质内酪氨酸羟化酶免疫阳性神经元的数量。结果 模型组大鼠右侧黑质内可见稀疏的酪氨酸羟化酶免疫阳性神经元,神经元内大量表达人α-突触核蛋白,部分人α-突触核蛋白呈聚集样表现。与模型组大鼠相比,模型+跑台训练组大鼠黑质内酪氨酸羟化酶免疫阳性神经元残存率显著升高(P=0.000)。旷场实验中,与模型组大鼠相比,模型+跑台训练组大鼠的穿梭距离(P=0.001)、下肢站立次数(P=0.031)和总跑动时间(P=0.007)均显著增大。前肢使用不对称测试中,与模型组大鼠比较,模型+跑台训练组大鼠的不对称指数显著减小(P=0.000)。阿扑吗啡诱导旋转实验中,与模型组大鼠比较,模型+跑台训练组大鼠的旋转圈数明显减少(P=0.017)。结论 跑台运动能够改善过表达人α-突触核蛋白偏侧帕金森病大鼠模型的黑质多巴胺能神经元退变和运动障碍表现。

关键词: 帕金森病, 跑台运动, α-突触核蛋白, 多巴胺能神经元, 大鼠