Correlation Between Vascular Endothelial Growth Factor (VEGF),Matrix Metalloproteinase-3 (MMP-3) And Interleukin-18 (IL-18) Expression In Synovium Of Collagen-induced Arthritis Rats (CIA)

Objectives:To observe the expression of vascular endothelial growth factor(VEGF),matrix metalloproteinase-3(MMP-3),interleukin-18(IL-18)in synovium of collagen-induced arthritis rats(CIA)at different time point,to investigate the significant difference between model group and healthy control group,the correlation among VEGF,MMP-3,IL-18,to explore the role of them in CIA and to understand the pathogenesis of rheumatoid arthritis(RA)thoroughly. Methods:Forty-two male Wistar rats were randomly divided into 2 groups(each 21), namely the model group and the normal control group.Cattle Collagen typeⅡ(CⅡ)and complete Freund's adjuvant were used to induce experimental arthritis(CIA)contrast with isotonic Na chloride.The accumulated points of arthritis index was evaluated based on degree and extent of flare and the condition of tumefaction and deformation.According to the degree of Synovitis and synovium thickening,condition of granulation tissue,corrosion of bone and cartilage,we carry on the histological scores.The higher the accumulated points of arthritis index and histological scores were,the more serious the arthritis symptom was.expression of VEGF,MMP-3,IL-18 were obtained by immunohistochemical analyses.The histological scores were detected by hematoxylin and eosin stain..These cytokines were assayed simultaneously at different time point and changes between arthritis index(AI),histological scores and these cytokines were observed along the time course.The expression of VEGF,MMP-3,IL-18 were assayed by factorial analysis at different time point.The correlations between those of VEGF,MMP-3,IL-18,AI,histological scores and these cytokines were analyzed with linear correlation analysis and rank correlation analysis respectively.Results:Forty-two rats attended the experiment,all of them entered the final analysis.The neovasularization of synovium was increased,synovium was thickening,the accumulated points of arthritis index and the histological scores were gradually increased,and the level of VEGF,MMP-3,IL-18 were increased accordingly with the process of the invasion time of the CIA. These cytokines are significantly higher in CIA group than control group(p＜0.01).AI and the histological scores had the positive correlation with the level of expression of VEGF,MMP-3,IL-18(p＜0.05),and these cytokines had a positive correlation(p＜0.01)too.Conclusion:VEGF,MMP-3,IL-18 are related closely with the course of CIA,and play important roles in generation of synovits,formation of pannus and corrosion of bone and cartilage.They develop into a complex network,mutually influenced and made CIA develop continually,and may be the key factors among multiplicate ones which mediate the generation,development,bone destruction and function barrier of RA.