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ObjectiveTo investigate the feasibility and effectiveness, and expolre the possible meachanism of intra-articular arsenic trioxide injection for treatment on rats with collagen-induced arthritis.Methods71 Female Wistar rats were randomly divided into two groups: normalcontrol group(11 rats,groupⅠ) and model group(60 rats),which were induced for CIA model. The CIA rats which the arthritis index(AI) was above three,then were randomly divided again:PBS control group(14 rats,groupⅡ) and arsenic trioxide(ATO) treat group(16 rats,groupⅢ).Their ankle joints were injected with 0.1ml PBS and 10% ATO respectively,at the same time ankle joints of groupⅠwere also injected with 10% ATO. they were all done once every three days,a total of four times,then were killed after three days of the last injection. All rats were assessed from body weights,arthritis index,posterior paw thickness , ankle circumferences, synovium thickness of high frequence ultrasound before CIA model, before and after intra-articular drug injection.They were compared of X rays before and after drug injection.Finally,the specimen were observed by H-E stain ,couting the scores, and detected the expression of Nuclear factor Kappa B(NF-κB) and vascular endothelial growth factor (VEGF) by immunohistochemistry. As well,the serum interleukin-1(IL-1) and tumor necrosis factor alpha (TNF-α) levels were tested by Enzyme-Linked immunosorbent Assay (ELISA).Results1.The weights of model group(groupⅡand groupⅢ) were more than before CIA established ,but the speed was slower than that of normal control group (groupⅠ)(P <0.05). After intra-articular drug injection,the weights of all groups decreased, but showed no stastistically significant differences among them(P>0.05).2.Compared with groupⅠ,The arthritis index, posterior paw thickness,ankle circumferences, synovial thickness of high frequence ultrasound of model group(groupⅡand groupⅢ),were higher than that before CIA established (P<0.05). They were all lower ingroupⅢ(P<0.05), while no consipious decline in groupⅡ(P>0.05) after intra-articular drug injection .Compared between groupⅡand groupⅢ, they showed stastistically significant differences(P<0.05).3.Compared with groupⅠ,X rays of model group(groupⅡand groupⅢ) showed soft tissue swelling, some bone destruction, and H-E staining showed heavy inflammatory cell infiltrated , synoviocytes increased, new vascular developed.But after intra-articular drug injection , X scores showed no stastistically significant differences(P>0.05)between groupⅡandⅢ, while pathology scores had stastistically significant differences(P<0.05), the scores of groupⅢwere less than that of groupⅡ.4.The serum IL-1, TNF-αlevels ,and the expression of synovial NF-κB,VEGFin groupⅢwere all weaker than that in groupⅡ(P<0.05).5.There were no changes of above indicators in groupⅠbefore and after intra-articular ATO injection.Conclusions1.In CIA model, it can relieve joint syptoms and reduce synovial membrane pathological changes by intra-articular injection ATO.2.The mechanism of ATO maybe due to reducing the release of inflammatory cytokines, down regulation the activity of NF-κB and inhibiting the formation of VEGF .
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