Early Stage Of Antigen-induced Arthritis In Rabbits: A Comparative Study Between High-resolution Ultrasound, VEGF, TNF-a And Pathologic Findings

Background : Rheumatoid arthritis(RA) is a chronic immune-mediated inflammatory polyarthritis, leading toward joint functional impairment, structural damage. In previous studies, Doppler ultrasonogrphy(PDUS) and other imaging methodology had been used to evaluate the scale of arthritis on Antigen-induced arthritis model(AIA) model; however, the data focusing on pre-clinical and early stages of arthritis is limited. Ultimately, the animal models were sacrificed, for observing the destruction of joints and acquiring pathology samples purpose. It is difficult to acquire pathology samples of preclinical and early stage AIA arthritis in vivo.Purpose: To evaluate early stages of arthritis in AIA model in vivo, by using high frequent PDUS, serum VEGF, TNF-a and pathology evaluation. The efficiency evaluation of PDUS and serum biomarker were compared, by using synovial pathological sections as golden standard. We also estimate the feasibility and safety of US guided biopsy on AIA model, instead of animal sacrifice.Materials and Methods: 25 New Zealand white rabbits were randomlized into 2 groups, 20 in experimental group and 5 in contrast group. High-resolution ultrasound was used to evaluate the thickness of synovial membranes, synovial color and cartilage 24 hours, 3 days, 7 days and then every week after model preparing. Serum VEGF and TNF-a were determined by Enzyme linked immuosorbent assay(ELISA). Ultrasound guided biopsy was applied and the pathological sections were observed by microscope and accessed by V.Krenn score system.Results: 1. The thickness of membranes, VEGF, TNF-a in animal model group were significantly higher than those of control group(P<0.05). 2. The stage of arthritis of AIA model includes prophase(0-72 hours), acute stage(72 hours-4 weeks), subacute stage(4 weeks-8 weeks) and chronic stage(8 weeks later). 3. In the prophase and acute stage, the thickness of membranes in animal group is thicker than that of control group(P<0.05). There is no significant different for serum VEGF and TNF-a level between these two group(p=0.789). 4. In the early stage(4 weeks-8 weeks) of AIA model, the thickness of membranes was with highest correlation with patholology score(R=0.871, P<0.05). 5. The success rate of US-guided biopsy was 95% and no infection, heamorrhage and bony destruction were observed after this procedure.Conclusion: 1. AIA model can be used as a stable model for the early stage of antigen induced arthritis. 2. For the observation indexes, in prophase,acute stage and subacute stage of this model, the thickness of membranes was better than VEGF and TNF-a serum biomarker. 3. US-guided biopsy is safety and effective method to obtain synovial membranes. 4. The stage of AIA model includes prophase, acute stage, subacute stage and chronic stage.