Study On The Effect Of Aerobic Exercise Combined With Naringenin In Multiple Sclerosis

PurposeTo investigate the effects and its mechanism of different intensity aerobic exercise combined with naringenin on multiple autoimmune encephalomyelitis（EAE）in experimental animal model of multiple scloresis（MS）.Method6-8 week C57BL/6J female mice were randomly divided into exercise（control）group（Con）,moderate intensity exercise group（ME）,high intensity exercise group（HE）,moderate intensity exercise+naringenin group（ME-Nar）,high intensity exercise+naringenin group（HE-Nar）,naringenin group（Nar）.Medium intensity exercise group load nothing（ME）and high-intensity exercise group load 4%of weight（HE）do the swimming training;naringenin group（Nar）use of naringenin（10mg/kg weight）by gavage;moderate exercise+naringenin group（ME-Nar）,high intensity exercise+naringenin group（HE-Nar）received swimming with naringin.After subcapsular injection of MOG_35-55 combined with complete Freund’s adjuvant（CFA）,the EAE animal model was induced in C57BL/6 mice with different intensity of aerobic swimming.From day 0 of exercise,6 days per week,And the weight of the mice was recorded and scored clinically every morning.The spleen,brain and spinal cord,peripheral and inguinal lymph nodes were isolated from the central nervous system by flow cytometry on the 14th or 30th day of the experiment.The CD4+T cells were detected by flow cytometry Subgroups,Th cell subsets,and ELISA to detect inflammatory cytokines and neuroprotective factors BDNF.Result1.Clinical scores:Compared with the control group,the patients with moderate intensity exercise group had no significant difference（P>0.05）.Compared with the control group,the clinical symptoms of EAE mice were significantly improved（P<0.05）.There was a significant difference between the two groups（P<0.05）,the two groups(including moderate exercise intensity+naringenin group,（P<0.05）.There was a significant difference between the moderate exercise group and the high intensity exercise group（P<0.05）.There was significant difference between the moderate exercise intensity and the naringenin group and the high exercise intensity and naringenin group（P<0.05）,Combined with naringenin to improve the clinical score of EAE（compared with Nar and large intensity）.2.Compared with the control group or the naringenin group,the high intensity aerobic exercise reduced the infiltration of inflammatory cells and the production of proinflammatory cytokines IL-17A,IFN-γand IL-1βin the central nervous system of EAE mice,increased the expression of antiinflammatory cytokines IL-10 and TGF-βto the contrary,but it did not affect BDNF and IL-6 production,and this effect can be enhanced by naringenin intervention;but moderate-intensity swimming exercise does not reduce inflammation in the central nervous system,the expression of cells and inflammatory factors affects the development and progression of EAE,but its effect has not been altered by naringenin.3.Compared with the control group,high-intensity aerobic exercise can regulate the balance of proinflammatory Th1 and Th17 cells and anti-inflammatory Treg cells in the central nervous system of EAE mice and alleviate the development of EAE,which inhibits the action of Th1 and Th17 Can be further enhanced by the naringenin intervention.But it did not further affect the Treg cells;and moderate intensity of aerobic exercise did not change the EAE mouse CNS Th cell subpopulation balance,and the combination of naringenin and can not co-change Th Cell subsets balance.4.Compared with the control group,high-intensity aerobic exercise can reduce the number of naiveT（Tn）cells in spleen cells,and increase the number of memory T cells（Tem）,but does not affect the central memory T cells（Tcm）And the moderate intensity aerobic exercise,naringenin intervention and the combination did not change the number of Tn,Tem and Tcm;5.Compared with the control group,naringenin and high-intensity aerobic exercise inhibited the number of Th1 and Th17 cells in the spleen of the peripheral organs,but only the high-intensity aerobic exercise increased the number of Treg cells;but moderate-intensity aerobic exercise did not affect the balance of Th cell subsets;naringenin combined with high intensity aerobic exercise further inhibited the number of proinflammatory Th1 and Th17,but not only to increase Treg cells.In conclusion1.High-intensity aerobic exercise combined with naringenin alleviate the clinical symptoms and progression of EAE mice,reducing the pathological changes of EAE to the brain and spinal cord of the experimental rats,and it is superior to the simple high-intensity aerobic exercise and naringenin treatment.2.IL-6,IL-17A,IL-1β,IFN-γand anti-inflammatory cytokines IL-10 and TGF-βin EAE mice were significantly inhibited by high intensity aerobic exercise combined with naringenin And the effect is superior to the simple high-intensity aerobic exercise and naringenin alone intervention group.3.High intensity aerobic exercise combined with naringenin can effectively inhibit the number of proinflammatory Th1 and Th17 cells and relieve the clinical symptoms of EAE,and the effect is better than the simple high-intensity aerobic exercise and naringenin alone intervention.