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Effects Of Anti-TCRαβ Monoclonal Antibody On Rheumatoid Arthritis Induced By Bovine Type Ⅱ Collagen In Mice.

Posted on:2008-04-19Degree:MasterType:Thesis
Country:ChinaCandidate:J X ChengFull Text:PDF
GTID:2144360218955719Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
PartⅠEstablishment of experimental rheumatoid Arthritis model Induced by bovine typeⅡcollagen (BcⅡ) in mice.Objective To establish and explore the characteristic of collagen-induced arthritis (CIA) model induced by bovine typeⅡcollagen (BcⅡ), and aim to provide experimental value for the further study.Methods 1,DBA/1 mice received intradermal injection at the base of the tail (2-3cm from the body ) with 100ul emulsion containing BcⅡplus complete Freund's adjuvant (CFA)。2,The features of the arthritis were evaluated by incidence rate,swelling extent|,inflammation index and body weight. 3,The features of the arthritis were evaluated by histological changes and radiological examination.Results 1,Red swellings could be observed at 28 days after immunization, at 39 days were the most conspicuous, and then gradually declined from the 53 days. compared with the solvent control group, distinguished difference could be observed (P<0.05). 2,The incidence rate of the model group was 100%, All of the mice immunized with developed. 3,The pathologic results showed the inflammatory cell infiltrate surrounding the vascellum and synovium hyperplasy, radiological examination showed joint surface not smooth and soft tissue obviously dropsy.Conclusion The susceptible inbred DBA/1 Mice could be induced to ideal rheumatoid arthritis model successfully. Based on the pathogenetic features, histopathologic changes and X-ray examination , the above animal model could more sufficiently mimic the typical characteristics of human rheumatoid arthritis and is suitable for experimental research on rheumatoid arthritis。PartⅡ. Inhibitory effects of anti-TCRαβMonoclonal antibody on collagen-induced arthritis in mice.Objective To present study was to explore the therapeutic effects of anti-TCRαβMonoclonal antibody on collagen-induced arthritis in mice(CIA) from the onset feature ,clinical appearance and immunological.Methods Male DBA/1 mice were randomly allocated to collagen induced arthritis group, anti-TCRαβMonoclonal antibody group and dexamethasone-treated group respectively .All the model DBA/1 mice injected intradermally at the base of the ail of typeⅡcollagen in an equal volume of complete Freund's adjuvant to induce arthritis were studied through assessment of clinical features and histopathological changes。Results The results showed that Monoclonal antibody can inhibit the hind paw edema and improve the general symptoms on CIA. As compared with model group, anti-Monoclonal antibody group significantly reduced inflammation index swelling index, incidence rate. The histopathological showed that decreased synoviocytes proliferation and slight pathological changes in synovial tissue and the formation of pannus.Conclusion The result indicated the anti-inflammatory properties of anti-TCRαβMonoclonal antibody on mice collagen-induced arthritis, Collagen-induced arthritis (CIA) is an animal model of rheumatoid arthritis (RA) that is widely used to address questions of disease pathogenesis and to validate therapeutic targets.PartⅢMechanism of Anti-TCRαβMonoclonal antibody to treat rheumatoid arthritisObjective To establish the DBA/1 mouse model Induced by bovine typeⅡcollagen (BcⅡ) whose mechanism is similar to rheumatoid arthritis .To Investigate the possible therapeutic effect on rheumatoid arthritis (RA) by detecting the effects of anti-TCRαβMonoclonal antibody on the immune function of IFN-γ, TNF-αand IL-4 levels from the immunological aspects.Methods The experimental arthritis was induced by intradermal injection of bovine typeⅡcollagen emulsified complete Freund's adjuvant in mice. The mice then given intra-abdomen injection with anti-TCRαβMonoclonal antibody and Dexamethasone . The levels of serum IFN-γ,TNF-αand IL-4 were detected by Luminex200 Liquid Array appraisement color-coded microsphere or bead.Results In this experiment, CIA model group induced by collagen was decreased by monoclonal antibody and dexamethasone, and have some inhibition effect on immunity. Luminex Liquid Array results show that the levels of IFN-γ,TNF-αin serum of CIA model group were higher than that normal group, which have significant difference from that in control group(P<0.01),anti-TCRαβMonoclonal antibody can lessen the higher level of IFN-γ,TNF-αin serum. All that indicated that cytokine had some effect on the pathogenesis of CIA.onclusion Cytokine was significantly involved in the collagen-induced arthritis, and anti-TCRαβMonoclonaI antibody has protective effects on the inflammation and its mechanism was probably related to abnormal immunoregulatory function, then downregulating the expressions of inflammatory cytokines, and relieve the inflamed injuries.
Keywords/Search Tags:Collagen-induced arthritis, Cytokine, Monoclonal antibody, Immunoregulation
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