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The Effect Of Triptolide On Interferon-gama(IFN-γ), Interleukin-10(IL-10), Transforming Growth Factor-β1(TGF-β1) And So On In Experimental Autoimmune Encephalomyelitis(EAE) Mice

Posted on:2011-08-06Degree:MasterType:Thesis
Country:ChinaCandidate:X R RenFull Text:PDF
GTID:2144360305978766Subject:Neurology
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Objective:In order to explore effective therapeutics for multiple sclerosis (MS) and to investigate the immune mechanism of experimental autoimmune encephalomyelitis (EAE), we design to treat EAE by triptolide (Tri).Through observating the expression of some kinds of cytokines, like IL-10, IFN-y, TGF-β1, TNF-a and IL-12, which are secreted by Th1,Th2 and Th3.Methods:Forty-five female C57BL/6 mice were randomly divided into EAE group (15), Tri treatment group (15) and adjuvant group (15). EAE model was established with MOG35-55. Tri was intraperitoneally injected in the dosage of 50μg/(kg-d) in treated group from day 5 post-immunization (p.i.), and mice in EAE and adjuvant group injected with normal saline as control. The symptoms of mice in EAE were monitored in accordance with the international standard of 5-score-system. Mice were sacrificed on days p.i.38-40. The spinal cords were dissected and were removed for paraffin section. These sections were used for HE staining, LBF myelin staining and IL-10, IFN-y, TGF-β1, TNF-a and IL-12 immunohistochemical staining. All the Data were analyzed with SPSS13.0 software.Result:1. EAE Models induced by MOG35-55 of C57BL/6 mice were established successfully. HE staining showed typical "muff-like" inflammatory cell infiltration in spinal cords. LBF myelin staining also showed demyelination. The differences of incidence, change of body weight and mean maximum clinical scores between EAE group and Tri treatment group were statistically significant(P<0.05). The inflammatory cell infiltration and demyelination was significantly decreased.2. There were expression of IL-10, IFN-y, TGF-β1, TNF-a and IL-12 in all three groups. After the intervention of Tri, compared with adjuvant group, the levels of IFN-y, TNF-a, IL-12 in EAE group were increased (P<0.05). The level of IL-10,TGF-β1 were decreased (P<0.05). Compared with EAE group, IFN-y, TNF-a, IL-12 in Tri group were decreased (P<0.05), and the level of IL-10, TGF-β1 were increased (P<0.05).Conclusion:1. Tri could suppress EAE by significantly decreasing incidence rate, relieving clinical severity and lessen inflammatory cell infiltration.2. It may be one of the mechanisms of Tri to treat EAE that depressing IFN-y, TNF-a and IL-12 secreted by Thl and promoting IL-10 secreted by Th2, which could regulate Thl/Th2,and promoting TGF-β1 to strengthen regulatory T cells'Function.
Keywords/Search Tags:Experimental autoimmune encephalomyelitis (EAE), Triptolide (Tri), transforming growth factor-β1 (TGF-β1), tumor necrosis factor-a (TNF-a), Interferon-gama (INF-γ), interleukin-12 (IL-12), interleukin-10 (IL-10)
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