跑轮运动对多发性硬化动物模型神经保护作用中的Rho激酶机制研究

Clinical trials suggested a disease-modifying effect of exercise in multiple sclerosis. Wheel running can delay the onset of the animal model EAE mice and alleviate the symptoms. The neuroprotective effect of wheel running has been suggested on EAE mice. The purpose of the project is to explore the effect and mechanism of wheel running to protect neurological function of EAE mice. We propose the hypothesis that wheel running may influence the modulation of immune cells and promote synapse regeneration through alteration of downstream molecules of the signal pathway of Rho kinase (ROCK). .The project will apply schemed voluntary wheel running in EAE mice, and compare the outcomes of different running programs: pre-EAE, post-EAE, and sequential running. The outcomes are evaluated by the time of onset, symptom scale, body weight and running miles. The infiltration of CD4+T cells in lesions and the alteration of axon and synapse after running will be investigated to reveal the neuroprotective effect of wheel running. The activation of ROCK and the phosphoration level of downstream molecules will be evaluated in brain and spinal cord. To survey the functional change of microglial and cytokines, the expression of M1/M2 phenotype marker will be investigated. The project will offer a theoretical and experimental basis for management of rehabilitation of multiple sclerosis.

临床研究提示运动对多发性硬化有潜在的疾病调节作用。动物模型EAE小鼠进行跑轮可延缓发病时间，减轻症状，可能有神经保护作用。本项目拟探索自主跑轮运动对EAE小鼠神经功能的保护作用及机制，并提出假说：自主跑轮运动可能通过Rho激酶（ROCK）及下游分子调节免疫细胞功能，促进神经突触再生，从而改善EAE神经缺损，延缓疾病进展。. 项目采用不同组合的自主跑轮运动（免疫前、免疫后及序贯运动），观察和比较其对EAE小鼠发病时间、症状（临床评分、体重、运动量）的影响；检测各组动物脑和脊髓组织炎性细胞浸润，轴索和突触标记蛋白表达，了解跑轮运动的神经保护作用；检测脑和脊髓组织ROCK表达及其底物的磷酸化水平，了解跑轮运动后EAE小鼠ROCK通路的变化；检测小胶质细胞不同表型（M1/M2）标记分子和细胞因子的表达，了解跑轮运动对小胶质细胞的调节作用。本项目将为多发性硬化的运动康复治疗提供理论和实验依据。