Focal Adhesion Kinase (FAK) Impact On Rats Collagen-induced Arthritis In The Pathogenesis And Drug Intervention

BackgroundRheumatoid arthritis (RA) is a mutilation autoimmune disease. The Most majorpathologic features of rheumatoid arthritis is the new joint synovial blood vessels andthe blood vessels of the strong on joint damaging. Cell proliferation and apoptosis arebalanced to maintain the stability of the cells in normal physiological function andquantity.Synovial fibroblasts involved in inflammation and angiogenesis of the entireprocess, which plays a key role in the process of the synovial pathologyFocal adhesion kinase (FAK) is a widely expressed non-receptor protein tyrosinekinases in the cytoplasm, located in the integrin protein aggregation at a variety offunctions, to promote cell proliferation, migration, and survival RA synovium intofiber cells of origin of invasive growth in its proliferation out of control. To apoptosis,the synovial membrane into the fiber cells have the characteristics of the tumor-likeproliferation of the synovial lining layer is difficult to detect. Thus we assume thatinhibition of FAK to reduce the occurrence of synovial cell adhesion, proliferation,and walk, etc., so as to achieve the goal of treatment of RA.This issue through the establishment of collagen-induced arthritis rat model toinvestigate the significance of focal adhesion kinase expression in synovial cells fromapoptosis and cell cycle control point of view of its collagen-induced arthritis in rats(by collagen induced arthritis,the CIA) the possible mechanism of action,and byobserving the changes in synovial cells of CIA rats before and after drug interventionlevel of FAK expression, to explore the mechanism of action of the combinationtherapy. In order to provide the experimental basis for clinical combination therapy inrheumatoid arthritis. ObjectiveIn this study, by observing the CIA rat synovial cells of RA animal models offocal adhesion kinase (FAK) expression, and observe the changes of FAK expressionlevels of drug intervention, to explore the mechanism of focal adhesion kinase in thepathogenesis of rheumatoid arthritis and joint treatment.MethodsEstablish Ⅱ collagen type of induction fem ale SD rats C IA m odel, randomlydivided into normal control group, CIA model control group, MTX treatment group(0.9mg.kg-1.w-1), CTX intermittent treatment group (24mg.kg-1.3w-1), LEF thetreatment group (1.2mg.kg-1.d-1), combined treatment group (two two joint MTX:0.9mg kg-1.w-1., CTX:24mg kg-1.3w-1, LEF:1.2mg. kg-1.w-1). For nine weeks invivo, began to medicine afte the first time immune three weeks.In the process ofcontinuous treatment of the rats joint inflammation levels grading, vernier gauges canmeasure the degree of the foot right hind leg. Treatment for six weeks after all animalsdrawn to be put to death, then the fixed, take off calcium, embedding and made intoslice. The rat line HE dyeing observation of the synovial ankle histopathologic change,further by immunohistochemistry methods were used test the CIA rats synovial cellsFAK expression level.Results1. CIA rat made model success rate was91.3%（72/78）, Symptoms, imaging,pathology evaluation model that made success, for chronic arthritis.2. Arthritis index（AI）：The treatment group which is AI obviously improve themodel group, the combination group is better than the single drug group MTXand LEF, CTX group（P＜0.05）.The joint between treatment group and thesingle drug between group without difference (P>0.05). The combination groupfoot the degree improve degree the most obvious (P <0.05).3. X-ray radiography: X-ray changes of the treatment groups compared with modelgroup for the light. Combined treatment group than the monotherapy group,Between each monotherapy group and combination therapy group, no difference,the combination therapy group X-ray change the minimum. 4. HE joint pathological changes: Synovial level in the CIA model group ratsincreased up to8layers, even more than10layers, disorganized, andinflammatory cell infiltration, cartilage, bone tissue is severely eroded. Themonotherapy group of MTX, LEF and CTX treatment group synovitis, cartilageand bone erosion has been reduced; synovitis of the combined treatment group,cartilage and bone erosion was significantly improved,5. Immunohistochemical method to detect the CIA rats in each group in synovialtissue FAK expression: Normal control group can be seen a small amount and nobrown yellow particle deposition, FAK expression was negative; modeling,control synovial cells within the group can be seen a large number of brownparticle deposition, FAK expression was strongly positive; the synovial cells ofthe combined treatment group can be seen a small amount of brownparticlesdeposition, expression of FAK positive; monotherapy group can be seena large number of brown particles deposition of FAK expression is positive.Conclusions1. FAK promotion of CIA rats synovial cell proliferation, inhibition of apoptosis ofsynovial cells, suggesting that FAK may be involved in the pathogenesis of RA.2. Immunosuppressants after the intervention can reduce the expression of FAK.Synoviocytes after joint intervention FAK expression significantly was inhibited,suggesting that combination therapy is more effective promote to apoptosis ofsynovial cells.