| Objective:Multiple sclerosis(MS)is a predominantly T-cell-mediated autoimmune disorder that results in inflammatory damage to the central nervous system(CNS).Infiltrates and demyelination are the main pathological changes in MS.The disability and difficulty in treatment have caused serious social impact in young adults.At present,hormone and immune inhibitor are the main durgs used in MS,but these drugs are all unsatisfactory because of their large side effects.Therefore,it is necessary to develop new drugs.Experimental autoimmune encephalomyelitis(EAE)model had provided an important basis for the study on the pathogenesis and therapy of MS.The pathological features of EAE are similar to MS.Involving the activation of lymphocytes and microglia,focal inflammatory demyelination and axonal damage.CD4+T cells,especially the Th1 and Th17 subgroups,have been suggested to cause the early initiation of the disease.Tanshinone ?A(Tan?A)is a bioactive component of DanShen and can be abundant isolated from it.A recent study found that in a brain injury model,inflammatory and the activity of the microglia could be inhibited by Tan?A,when the activity of regulatory T cells could be enhanced.The brain and spinal cord could be protected in that way.The aim of this study was to find the effects of Tan?A on the clinical manifestation and pathological changes of EAE,in order to provide the basis for the clinical application of Tan?A in MS.Method:EAE was induced by injecting an inoculum containing dissolved MOG35-55 in 6-8 weeks old C57BL/6 female mice.Animals were then randomly assigned to treatment group and control group.In the treatment group,200?l of Tan?A(25?mol/l)was injected intraperitoneally daily each mice while the control group was injected the same dose of PBS after onset.The weight and clinical scores of the mice were monitored everyday till all of them were sacrificed on the 26 th day.The inflammation and demyelination in the spinal cord were tested by HE and LFB staining,while the changes of lymphocyte subsets were analyzed by flow cytometer in the two groups.Results:Compared with the control group,the results showed that Tan?A could significantly decreased the clinical score and the severity of EAE.Tan?A injected could control the infiltrates and demyelination in the spinal cord of EAE showed by HE and LFB staining,the pathological score also decreased significantly(p<0.05).The flow cytometer analysis showed that,the percentage of CD4+T cells and the secretion of IFN-? and IL-17 related to Th1 and Th17 in the central nervous system mononuclear cells in the two groups were not significantly different(p<0.05);the secretion of IFN-? related to Th1 was decreased significantly in spleen in the two groups of EAE(p<0.05);the percentage of Treg in CD4+T cells increased in spleen,but has no statistical significance(p<0.05);the percentage of CD4+CD25+Foxp3+Treg in CD4+T cells in the CNS in Tan?A group was significantly higher than that in control group after MOG stimulation for 48h(p<0.05).Conclusion:Tan?A can significantly improve the clinical manifestations,reduce the severity of the disease,reduce the degree of infiltraties and demyelination in the central nervous system of EAE mice.The results of flow cytometry showed that Tan?A could significantly decrease the percentage of Th1 cells in the spleen of EAE mice when increase the percentage of Treg cells in the central nervous system.It is suggested that Tan?A may play an role in regulating the immune balance of EAE mice by stimulating the secretion of MOG reactive Treg cells and in alleviating the inflammatory response of EAE.All in all,Tan?A is likely to has therapeutic effect in MS,this maybe a new direction for the development of new drugs in MS. |
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