Protective Effect of Norcantharidin on Collagen-Induced Arthritis Rats

Objective To observe the effect of norcantharidin (NCTD) on collagen-induced arthritis (CIA) rats. Methods Sixty Sprague-Dawley(SD) rats were randomly divided into 6 groups ( n =10): normal group, CIA model group(model group), NCTD low-dose group [1.35 mg/(kg•d)], NCTD middle-dose group [2.7 mg/(kg•d)], NCTD high-dose group [5.4 mg/(kg•d)] and methotrexate (MTX) group [1.8 mg/(kg/w)]. Anesthetized rats were sacrificed by luxation of cervical vertebra after 4 weeks of administration. The arthritis scores were evaluated twice a week. The pathological changes in the ankle joints of rats were observed by hematoxylin-eosin (H&E) staining. The serum levels of interleukin (IL) 1β, IL-6, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), IL-17 and transform growth factor (TGF) β were detected by enzyme linked immunosorbent assay (ELISA). The mRNA expression of retinoid-related orphan nuclear receptorγt (RORγt) and forkhead box P3 (Foxp3) in peripheral blood lymphocytes were confirmed by real-time polymerase chain reaction. Results MTX and high-dose NCTD not only decreased the arthritis scores but also alleviated the pathological changes in CIA rats’ ankle joints compared with the model group ( P <0.05 or P <0.01). All doses of NCTD significantly inhibited the serum levels of IL-6, IL-17 and TNF-α in CIA rats ( P <0.05). Only middle- and high-dose of NCTD prominently decreased serum IL-1β and TGF-β levels of CIA rats ( P <0.05). However, NCTD has no effect on vascular endothelial growth factor (VEGF) level in CIA rats. The Foxp3 mRNA expression in all NCTD groups were increased significantly than in the model group ( P <0.05). The mRNA expression of RORγt in NCTD high-dose group was decreased apparently in comparison with the model group ( P <0.05). Conclusions NCTD showed therapeutic effect on CIA rats by inhibition of cytokines and regulation of Th17/Treg cells.