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Research On Immunomodulatorymechanism Of Sinomentine On TLR2 And TLR4 Of Pattern Recognition Recepts In Surface Of Bone Morrow Dendritic Cells From RA Mice

Posted on:2016-10-15Degree:MasterType:Thesis
Country:ChinaCandidate:B B WangFull Text:PDF
GTID:2284330482473016Subject:Immunology
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Object:Previous studies found Sinomenine can affect molecular signal transduction and expression pattern recognition receptors downstream, but the mechanism is no more in-depth, this paper proposed hypothesis that Sinomenine can treat the rheumatoid arthritis by influencing pattern recognition receptors, RA animal by in vitro culture of bone marrow-derived DCs, exploring the impact of pattern recognition receptors from Sinomenine in RA mice, and evaluate its role in RA pathogenesis and disease progression, as Sinomenine Evaluation of postmarketing clinical and laboratory evidence provided.Methods:SPF level bal/c mice were established on the basis of literature modified collagen-induced arthritis model (CIA), after a successful model mice were sacrificed, according to the literature modified after a bone marrow-derived DC cultured On day 5 DC,maturation stimulus LPS was added at day 6, using flow direct immunofluorescence detection of the resulting cells CD11c, CD86 expression to identify DC cells. The training is divided into mature DC Sinomenine high-dose group, Sinomenine dose group, Sinomenine low-dose group, model group and the control group, methotrexate group, sinomenine group was given different concentrations Sinomenine,then using flow cytometry explored TLR2, TLR4 expression after 24 hours, and in cell culture supernatant was detected for IL-1, IL-10, TNF-α levels using elisa method. All the experimental data were statistically analyzed using SPSS 19.0 software.Results:1、bovine collagen type Ⅱ joint complete Freund’s adjuvant base of the tail of the mice, the abdomen, after footpad injection in about 35 days can induce RA model; 2, IL-4 and GM-CSF can be in the 5th days to induce bone marrow-derived cells into DC and DC in the training process often in aggregation state; 3, expression of TLR2, TLR4 in model mice was significantly higher than the control group of mice, sμggesting that rheumatoid arthritis processing may affect the TLR expression of murine BMDC surface; 4, after the intervention by Sinomenine can reduce mouse BMDC surface TLR2, TLR4 expression;5, Sinomenine able to reduce the secretion of IL-1/TNF-α; and 6, sinomenine can suppress DC maturation.Conclusion:Sinomenine by reducing DC surface expression TLR2, TLR4, the impact of downstream signal transduction pathways, so that the relevant reduction in the secretion of inflammatory cytokines, While suppressing DC maturation, thereby indirectly inhibit antigen presentation process, the impact of T lymphocyte activation,inhibition of the immune response, thereby preventing rheumatoid arthritis, chronic inflammation process occurs, so that destruction of the bone tissue is suppressed, in order to achieve the effect of treatment of rheumatoid arthritis.
Keywords/Search Tags:Sinomenine, rheumatoid arthritis, pattern recognition receptors
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