Objective   To establish the bovine collagenⅡ(CⅡ)-induced arthritis (CIA) rat model

and investigate the role of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in the pathogenesis of rheumatoid arthritis (RA).    Methods   Totally 50 SD rats were randomly divided into normal group (n=10) and 4 model groups (n=10 in each group). The model group was subjected to CIA by injecting 1 g/L CⅡ mixed with imcomplete Freund adjuvant into the skin of tail and back of the rats followed by the injection of half of dose in 7 d later. The rats of 4 model groups were sacrificed in 21

28

35 and 42 d after the first injection and their ankle joints were removed. The arthritis activity

pathological changes and expressions of HIF-1α and VEGF in the synovium at different time were observed through immunohistochemistry staining. The correlations of HIF-1α and VEGF expressions with the CIA arthritis activity indexes and pathological scores were analyzed.    Results   HIF-1α and VEGF were expressed in both the lining and sublining area of the synovium in CIA and the expressions had positive correlation obviously(r=0.75

P0.01). The results of immunohistochemical staining showed that the expressions of HIF-1α and VEGF in the synovial membrane were strongest on the 21st day

then declined gradually with the prolonged disease course. The expressions of HIF-1α and VEGF were correlated significantly with total pathological score

synovial hyperplasia score and angiogenesis score(r=0.4

0.48

0.50; P0.05)

but not with inflammation score(r=0.3

P0.05).    Conclusion   HIF-1α may promote the pathogenesis of rheumatoid arthritis

such as synovial hyperplasia and angiogenesis through inducing the expression of its target gene VEGF.