| Background:Rheumatoid Arthritis (RA) is a kind of chronic inflammatory disease that mainly influence synovial and joints. It is mainly characterized with synovial hyperplasia, joint pain, joint swelling, destruction of articular cartilage and bone.The disease mainly involves the hands proximal interphalangeal and can also occur in the small joints, such as wrist, foot in a symmetrical distribution. Its pathogenesis is still not clear yet. It is generally believed that its pathogenesis is related to heredity, infection, autoimmune and environmental factors. Lymphocytes, neutrophils, macrophages, synovial cells, cytokines and other inflammatory cells mediate abnormal cellular immunity and humoral immunity, which causes the local and systemic immune dysfunction and plays an important role in the pathogenesis of RA. Animal models of rheumatoid arthritis is a powerful tool for us to study the etiology, pathogenesis and treatment of RA. Now there are many types of animal models such as adjuvant arthritis(AA), collagen arthritis (CIA), etc. Borrelia burgdorferi is the pathogen of lyme disease. Mid and late lyme disease is mainly performed for chronic arthritis, nervous system and heart disease. Occurring rate of lyme arthritis is highest among all the symptoms.More than half of the patients develop arthritis symptoms.Lyme arthritis is similar with RA and react arthritis, so it can be used for studying these arthritis. Lewis, SD and CD-1 rats are often used for lyme disease animal model. Among them, Lewis and CD-1 rats are more sensitive.They can produce myocarditis and arthritis after infection. Lyme disease animal model is made through subcutaneous or intraperitoneal injection to the experimental animal. It has been found that after the host infected with burgdorferi, the quantity of burgdorferi drops rapidly. And with the number of burgdorferi drops, arthritis gradually reduces at the same time. Only infected with burgdorferi again, the body will appear stronger immune response and destructive arthritis. Gondolf KB et al’s study confirmed that the intra-articular injection of complex Borrelia burgdorferi outer surface proteins extracted with butanol can induce chronic arthritis in mice.Based on the background of lyme arthritis induced by borrelia burgdorferi, this experiment plans to explore the possibility of inducing RA by whole cell protein of burgdorferi and incomplete freund’s adjuvant.Objective:The animal model of rheumatoid arthritis was established in Lewis rats by double intradermal injections of whole cell protein of Borrelia burgdorferi.Methods:Lewis rats were divided into six groups, such as low-dose burgdorferi group, medium-dose burgdorferi group, high-dose burgdorferi group, complete freund’s adjuvant group, incomplete freund’s adjuvant group and saline group. The degree of pathogenicity and the pathological characteristics were assayed by arthritis index and histiopathological techniques. Serum cytokine producion was measured by enzyme linked immunosorbent assay(ELISA). The expression of MMP3 and TIMP1 were tested through immunohistochemistry.Results:16 days after second injection, the incidence of arthritis in high-dose burgdorferi group was 66.67%. As showed by histopathology, typical arthritis pathology such as synovial proliferation, articular cartilage and bone erosion were discovered. The cytokines, arthritis index, histopathological score, IHS score for MMP3 and TIMP1 of the high-dose burgdorferi group had no statistical difference compared with that of the complete freund’s adjuvant group (P>0.05); while statistical difference compared with that of the incomplete freund’s adjuvant group and saline group(P<0.05).Conclusion:1.0.1ml intradermal injection of 6mg/ml whole cell protein of Borrelia burgdorferi to right foot, two weeks later, intraperitoneal injection of the same dose and the same concentration, which can induce Lewis rats model of rheumatoid arthritis.The model building rate can reach 66.67%.2. The serum level of RF, TNF-a, IL-1β, IL-6 and IL-17 of whole cell protein of Borrelia burgdorferi induced arthritis model elevated.3. The MMP3 expression increased and TIMP1 expression decreased in whole cell protein of Borrelia burgdorferi induced arthritis model.Background:Rheumatoid Arthritis is a chronic progressive autoimmune disease. Environmental factors and genetic factors play a big role in the occurrence and development of disease. Genetic factors may be the base of RA. In recent years, tumor necrosis factor induced protein 3 (TNFAIP3) gene is a susceptible gene which is considered to be strongly correlated with rheumatoid arthritis in addition to HLA. TNFAIP3 also encodes ubiquitin-editing protein A20,which is an inhibitor of nuclear factor-kappaB, Interferon regulate factor 3 and tumor necrosis factor activation in several signaling pathways, including those of TNF, Toll-like and Nod-like receptors [3].In 2007, the wellcome trust case control association (WTCCC) genome-wide studies have found that tumor necrosis factor induced protein 3 gene rs6920220 and rs10499194 loci are associated with rheumatoid arthritis, then studies of TNFAIP3 increases.But the conclusions are not consistent.Objective:To validate the association between rheumatoid arthritis (RA) and TNFAIP3 gene polymorphism.Methods:Six SNPs in TNFAIP3(rs6920220、rs2230926、rs5029937、rs10499194、 rs2327832、rs13207033) which had been extensively examed were selected. Published studies on RA and TNFAIP3 were retrieved and a Meta-analysis was conducted.Results:A total of 18 studies with 27554 RA patients and 39664 controls were included. The comprehensive analysis showed that the gene polymorphism of rs6920220、rs2230926 and rs5029937 was associated with RA (P＜0.01, P=0.03, P＜0.01).The gene polymorphism of rs2327832 and rs13207033 was not associated with RA (P=0.27, P=0.05). The subgroup analysis showed that the gene polymorphism of rs10499194 was associated with RA in white people [OR=0.87 (0.80-0.95), P＜0.01]. The gene polymorphism of rs10499194 was associated with RA in yellow people [OR=1.28 (1.13-1.46), P<0.01].Conclusion:The Meta-analysis reveals that the gene polymorphism of rs6920220、 rs2230926 and rs5029937 was associated with RA. The association between the gene polymorphism of rs10499194 and RA had racial differences. |
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