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Study On Effects And Mechanism Of The Active Fraction Of Honghuoma In RA

Posted on:2009-07-27Degree:MasterType:Thesis
Country:ChinaCandidate:Y YaoFull Text:PDF
GTID:2144360278963806Subject:Pharmacology
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Objective: To identify the therapeutic effect of Chinese Medicine Honghuoma; to investigate the preventive effect of the active fraction of Honghuoma on CIA model and AA model; to explore the therapeutic effect of Chinese Medicine Honghuoma in RA by testing the expression of transcription factor in collagen-ⅱinduced adjuvant arthritis and adjuvant arthritis ratsMethod: (1)KM mice were divided into 4 groups. The doses are 10mg/10g,5mg/10g, which lasted 7 days. Honghuoma was administered every other day. The mice were suffered 50℃hot broad,0.6% acetic acid solution and xylene in auris dextra, the effect of antinflammatory and relieving pain was observed;(2)Collagen II induced arthritis was set up in BALB/c mice. The doses are 1.5mg/10g,1.0mg/10g,0.5mg/10g, which lasted 7 days. Honghuoma was administered every other day, the incidence of arthritis and injury inside the joint was observed。AA model rats induced by Freund's complete adjuvant (CFA) were treated with Honghuoma by gastric gavage 7 days before model established as the preventive group and 3 days after model as the treatment group. On the 39th day, spleen index and swelling degree of paw of rats were measured.(3) Serum levels of interferon gamma (IFN-γ), interleukin-2(IL-2), interleukin-4(IL-4) and interleukin-10(IL-10) were determined by enzyme-linked immunoabsorbent assay (ELISA).The expression of T-box expressed in T cells (T-bet) and GATA binding protein 3 (GATA-3) were detect by RT-PCR. The underlying mechanism was explored by detecting the phenotype of DC and mRNA level of DC T-bet.Result: (1)In the experiment study of the pain reaction of mice by hot stimulation, 1.5mg/10g,1.0mg/10g Honghuoma can significantly increase the threshold of pain(P<0.05);to the writhing test mice, writhing number of 1.5mg/10g,1.0mg/10g Honghuoma were much smaller than the control group,especially the high dose group(P<0.01);in the experiment study of the ear-swelling of mice induced by xylene, right paw swelling degree in rats of 1.5mg/10g,1.0mg/10g were significantly lower than the control group(P<0.01).(2) In CIA, after 40 days of treatment,the incidence of arthritis was significantly decreased by Honghuoma in a dose related manner, compared with that in the blank control group;In AA, Honghuoma could decrease the paw swelling and spleen index, improve the weight.(3) No inflammatory cells infiltration was found in synovium by histological analysis, and the interspace of joint was intact. T-bet mRNA level in bone marrow derived DC was down-regulated by 20mg/L Honghuoma,and the phenotype expression of MHC-II and CD86 on CD11c+DC was unaffected by Honghuoma by FACS analysis. Morever, honghuoma increased the expression of GATA-3 mRNA and decrease T-bet. Honghuoma could obviously decrease the serum levels of IFN-γ. Eventually Honghuoma in both preventive and treatment group could attenuate the symptoms of RA .Conclusion:(1) The active component of Honghuoma can relieve pain and be antiinflammatory agent;(2) the incidence of arthritis was significantly decreased by Honghuoma in a dose related manner.17.5mg/100g Honghuoma can treat the RA;(3) Honghuoma shows obviously preventive effects on CIA and AA model, and which is associated with the negative control of T-bet transcription and positive control of GATA-3.
Keywords/Search Tags:rheumatoid arthritis, CIA, AA, DC, T-bet, GATA-3, Honghuoma
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