| Objective: Multiple sclerosis(MS) is an commomn and chronicity disease of the central nervous system(CNS) with the characteristic that inflammatory reaction,demyelinate and axonal degeneration in the white matter . It causes recurrent attacks and progressive neurological impairment in CNS.At present it is considered that the chief pathogenesy of MS is the specificity stimulating T lymph cell aim at self NS medullary sheath. The secretion of the Th1 cytokines like TNF-α,IFN-γ,IL-1,IL-2 etc was reinforced , at the same time, the secretion of the Th2 anti-inflammatory cytokines like IL-4,IL-10 etc was suppressed. Most of the attention was paid to the immunosuppressants, but respecting to the side effect of the immunosuppressants, alternative treatment options are higly desired.Thymus is one of the most important center immune organ of the immune system, it in charges of the differentiate and ripening of T cells. ThymocrescinⅡis a single polypeptide cpds that was dissociated from human thymic hormone,which contains 49 amino acids. TpⅡleads the differentiation and ripening of T cell subgroups,reduce the production of the autoantibodies,adjusts CD4+/CD8+ and the immune system to a normal condition.Thymopentin-5 is a synthetical pentapeptide, which has the same amino acid sequence and structure with the 32-36 bit amino acids of ThymocrescinⅡ.TP-5 has the whole biologic activity of ThymocrescinⅡ.In our study, we administrate TP-5 to the rats of experiment allergic encephalomyelitis (EAE)-an animal model of MS, in order to investigate the therapeutic potential in treatment of neuroinflammatory diseases like MS.Methods: 130 female Wistar rats weighing 180-200 grams were divided into 5 groups, that is 10 rats for blank control group, and EAE group, low-dose treatment group (0.05mg/kg), high-dose treatment group (0.25mg/kg), daxamethasone treatment group, each group 30 rats. And the last 4 groups were divided into 5 smaller groups, that is 7days group, 14 days group, 17 days group, 21 days group and 28 days group, 6 rats for each smaller group.All experiment rats were immunized subcutaneously in the four footpads with emulsion 0.4 ml, which including fresh GPSCH as antigen, emulsified with an equal volume of CFA containing Mycobacterium tuberculosis 4mg/ml.Clinical signs of EAE was assessed a minimum of twice daily by two investigations. Scores were assigned on the basis of the following symptoms: 0,normal mouse; 1, piloerection, tail weakness; 2, tail paralysis; 3, tail paralysis plus hindlimb weakness; 4, tail paralysis plus partial hindlimb paralysis; 5' total hindlimb paralysis; 6, hind and forelimb paralysis; 7,moribund/ dead. During the experiment, the mean maximal score of animals at different time point and the incidence of disease were observed as results.EAE group left untreated, low-dose treatment group (0.05mg/kg), high-dose treatment group (0.25mg/kg), daxamethasone treatment group(5mg/kg).This treatment was started on the first day of immunization and continued daily for the duration of the experiment.Respectively on the 7, 14, 17, 21 and 28th day of immunization, quickly take surroundings of the lateral cerebral ventricle and neck, chest, lumbar segment of spinal cord. Inflammation and infiltration was assessed after HE dyeing. TNFR1,TNFR2,IL-10mRNA was determined by semi-quantity reverse transcription polymers chain reaction(RT-PCR).Results:1 The incidence of disease in different groupEAE group is higher than daxamethasone treatment group,low-dose treatment group and high-dose treatment group(P<0.05)2 Clinical profile of EAE in different groupCompare the neurofuction deficiency in the four groups, we found that EAE group was higher than the treatment groups(P<0.05)Histopathology findingsInflammatory cell infiltration in EAE groups was higher than the treatment groups(P<0.05). Daxamethasone treatment group is higher than the low-dose treatment group and high-dose treatment group(P<0.05)TNFR1,TNFR2,IL-10mRNA express level:TNFR1 step up at the catadrome of invasion, and keep ascensus following the progression of the disease. It began to drop at the convalescence stage. It was associated with the activity of EAE. The TP-5 treatment groups were lower than the EAE group and Daxamethasone treatment group at the crest- time and convalescence time(P<0.05)TNFR2 step up at the crest- time of the disease and arrival the highest at the convalescence time.It began to drop at the relapseing stage. It was associated with the activity of EAE. The TP-5 treatment groups were higher than the EAE group and Daxamethasone treatment group at the crest- time and the relapsing time(P<0.05)IL-10 step up at the catadrome of invasion, and keep ascensus following the progression of the disease. It began to drop at the convalescence stage. It was associated with the activity of EAE. The TP-5 treatment groups were lower than the EAE group and Daxamethasone treatment group at the crest- time and relapsing time(P<0.05)Conclusion: TNFR1,TNFR2,IL-10 in CNS of associated with the activity of EAE.ThymocrescinⅡreduces the incidence of disease in EAE rats, and protect the rats from the severity of the disease. Compared to dexamethasone, dexamethasone is better than ThymocrescinⅡin reducing the incidence and relapse in EAE at the catadrome of invasion. But at the crest- time and relapsing time, it is surpassed by ThymocrescinⅡ,especialy in the protecting of the nerve fibre.ThymocrescinⅡcan regulate immune function, suppress the expression of the phlegmasia medium so as to lesson the damage in CNS.ThymocrescinⅡpromote the expression of TNFR2 and IL-10, inhibits the expression of TNFR1.
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