| Objective: Rheumatoid arthritis (RA) is a kind of systemic autoimmunedisease with disabling arthritis as the main clinical manifestation, the diseasewith chronic, symmetry and destructive arthritis as the main characteristics, Themain affected target joints are proximal interphalangeal joints,metacarpophalangeal joint and wrist joint, such as temporomandibular joint,elbow, ankle also often affected.Some patients may also have fever, anemia,subcutaneous nodules and so on. The basic pathological characteristics of RA isthe chronic inflammation of synovial joints, in the early synovial hyperplasia ofcongestion, edema, and formation of pannus, result in synovial thickening,seepage, secrete a variety of cytokines, infringement of cartilage and bonedamage of the surrounding tendons, ligaments, synovial sheath and musclegroups also can be eroded, its damage is similar to the destruction of the tumor,including formation of new blood vessel and degradation of extracellular matrix,are two crucial steps in the process of destruction. Target of the treatment areeducing the release of inflammatory factors and inhibiting pannusformation.In a clinical context often use disease modifying anti-rheumatic drug(DMARDs)combined biological agents to prevent bone destruction anddelay.But biological agents treatment costs high, widely used have limitations. Recent studies suggest that artesunate as a semi-synthetic artemisinin derivatives,as a kind of potential immune inhibitors of low toxicity, high efficiency. Thestudy found that artesunate can suppress synovial cells induced by LPS of RAsecreted TNF alpha by adjusting the NF-kappa B signaling pathways. Whichwere play the role of inhibition of RA synovial inflammation. At the same timeit also can inhibit secretion of IL-17, TNF alpha and both collaborative effectto inhibit secretion of inflammatory factor by synovial cells, thus reducingformation of pannus and erosion of cartilage and bone.CD4+CD25+regulatory T cells (Treg cells) play a key role in maintaining the dynamicbalance of the immune system and preventing the occurrence of autoimmunediseases.Foxp3specific expression on Treg cells, and Foxp3is required in thedevelopment and function of Treg cells.Our subject established the male Wistar rats model with Ⅱ type collageninduced arthritis（CIA）, Explore the artesunate regulation function of Foxp3related signaling pathway activation,proposed to disscuss from the perspectiveof T lymphocytes transcription factors to explore whether artesunate viaincreased transcription factor Foxp3(forkhaed/winged helix transcription factor)to reduce the activity of IL-17, that has the effect of immune regulation. Clearthe treatment targeted of artesunate.Methods: Established the male Wistar rats model with Ⅱ type collageninduced arthritis（CIA）. Evaluating the degree by observing the index.Took outthe synovial and culture synovial cells to5-7generations, It was divided intonormal control group、CIA model group、different concentrations ofArtesunate’group、methotrexate（MTX）group、hydroxychloroquine group、methylprednisolone group.The gene expression of Foxp3in different synovialcells groups were detected by reverse transcription polymerase chain reaction(rt-pcr),the protein expression of different groups were detected by western blotting.Results:1. The success rate of building CIA model was90.3%(56/61).2. Evaluation index of clinical features: Model group rats had weight losscompared with normal rats,activities reduced and spirit was poor.Progression of arthritis symptom after building especially as the symmetrichind limbs joint significantly. The peak of arthritis performance appears in6weeks after the immune, then gradually into the chronic phase,Joint stiffnessand deformity.3. Molybdenum target X-ray: CIA rat of10weeks：osteoporosis、destruction ofarticular cartilage and bone, narrowing of joint space. CIA rat of21weeks：osteoporosis、destruction of articular cartilage and bone、Joint damage, partof them have subluxation.4. Gene expression: Fiber synovial cell reduced in the drug intervention of theCIA model group, expression of Foxp3increased, the difference betweengroups was statistically significant (P <0.05).Foxp3in20ng/ml artesunategroup were higher than the5ng/ml artesunate group、10ng/ml artesunategroup, MTX group, hydroxychloroquine group and methylprednisolonegroup(P <0.05).5. Protein expression:Hyperplasia of the synovial cells decreased in the drugintervention group from the CIA model group, Foxp3expression in the CIAmodel group increased, the difference between groups was statisticallysignificant (P <0.05). Foxp3in20ng/ml artesunate group were higher thanthe5ng/ml artesunate group、10ng/ml artesunate group, MTX group,hydroxychloroquine group and methylprednisolone group(P <0.05). Conclusions:1. In CIA rats models: More than six points in arthritis index (AI) scoring;Jointswelling degree，osteoporosis，bone destruction performance serious than thenormal group.2. Artesunate can increase the expression of T lymphocytes with Foxp3, Foxp3expression in the collagen induced arthritis rats synovial cells significantlyincreased with the increase of the dose,was positively related with dose.Foxp3in20ng/ml artesunate group was higher than those in other groups,which suggests that may by raising expression of Foxp3in synovial cells andinhibiting secretion of inflammatory cytokines, thus reducing formation ofpannus and erosion of cartilage and bone, involved in the pathogenesis andpathological changes of RA. |
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