Impact Of Cycle Combined With Methotrexate And Cyclophosphamide On The Expression Of FKN And CX3CR1of CIA Rats’s Synovium

BackgroundRheumatoid Arthritis (Rheumatoid arthritis, RA) is a kind of mutilation arthritis. Histologically, it is characterized by hyperplasia within the synovium. The intimal lining of the synovium also displays remarkable changes in RA, with a marked increase in cellularity. The lining expands from1-2cells deep to a depth of up to10-20. Hypercellularity is due to an increase in fibroblast-like synoviocytes (FLS). At present, the cause of the tumor-like changes of FLS may be that chronic inflammation may obtain a certain degree of autonomy, that is to say after the T cell inflammatory response down, FLS can still make the inflammation persists.FLS stimulate autocrine growth by releasing FKN and triggering the activity of their own CX3CR1.Through over ten years clinical research, we observed that the therapeutic alliance of methotrexate(MTX) and cyclophosphamide (CTX) had a better curative effect in treating RA. In our previous research, combination MTX with CTX can more significantly delay joint damage in RA. The alliance of MTX and CTX had synergistic effect inhibiting proliferation of synovial cells.They also had synergistic effect in animal studies. But it is indefinite whether the therapeutic alliance of MTX and CTX synergistically suppress FKN-CX3CR1expression of RA synovial cells. We will give the answer by observing the dynamic level of the FKN-CX3CR1in different theraputic groups. ObjectiveIndefinite whether the therapeutic alliance of MTX and CTX synergistically suppress FKN-CX3CR1expression of RA synovial cells.MethodsThe study was an animal experiment. DBA1male mice were included. Establish II collagen type of induction CIA model, randomly divided into CIA model control group, MTX treatment group(0.9mg.kg-1.3d-1), CTX intermittent treatment group (24mg.kg-1.10d-1), combined treatment group (MTX:0.9mg.kg-1.3d-1, CTX:24mg.kg-1.10d-1). DMARDs were treated after3weeks of C Ⅱ immunization. In the process of continuous treatment of the rats, we need measure the degree of the right hind ankle swelling and arthritis index score. After treatment for three and seven weeks, animals need to be put to death, and then made into slice. Observing the pathological changes by HE and safranin-fast green staining. Further by immunohistochemical detection of synovial tissue FKN and CX3CR1, using Image-Pro-Plus6.0image analysis software analysis system for measuring the optical density of the accumulated positive area and the average optical density.Results1. After3weeks of treatment, the joint swelling, AI of each treatment group improved significantly than the CIA group, and there are statistical significance. Some of the combined group improved significantly than the single drug group, the difference was statistically significant.2. At the time of three weeks treatment, arthritis pathology score of each treatment group were dissimilar to the CIA group. At the time of seven weeks treatment, differences in the arthritis pathology score between the treatment groups and the CIA group was statistically significant, but the differences between the treatment groups was not statistically significant.3. At the time of three weeks treatment, the FKN expression in synovial tissue of each treatment group was dissimilar to the CIA group. At the time of seven weeks treatment, differences in the FKN expression between the treatment groups and the CIA group was statistically significant, and differences in the FKN expression between the combination group and some single-drug groups was statistically significant.4. At the time of three weeks treatment, differences in the CX3CR1expression between the combination treatment group and the CIA group was statistically significant, but there was no statistically significant difference between some single-drug groups and the CIA group. At the time of seven weeks treatment, differences in the CX3CR1expression between the combination treatment group and the CIA group or most single-drug groups were statistically significant.Conclusions1. Combination group compared with single-drug group can more effectively improve the CIA joint swelling in mice, reducing arthritis index, relieve arthritis pathology;2. Combination group compared with single-drug group can more effectively inhibit the expression of FKN and CX3CR1synovial tissue, suggesting that the combined group can play better efficacy may influence the FKN-CX3CR1pathway to achieve.