Zhihuang Tongfeng decoction ameliorates gouty arthritis via inhibition of NLRP3 inflammasome in rats

摘要

Purpose: To investigate the effect and mechanism of action of traditional Chinese medicine, Zhihuang Tongfeng decoction (ZTD), on gouty arthritis in rats. Methods: Monosodium urate (MSU) crystal was injected into the ankle joint of rats to establish an animal model of gouty arthritis. ZTD (4.8, 9.6 and 19.2 g/kg) was administered to the rats. The walking behavior of the rats was observed daily and the gait score computed. Histopathologic severity was scored using three parameters, viz, synovial inflammation, synovial hyperplasia and cartilage surface erosion. The levels of IL-1β and TNF-α in lavage fluid of articular cavities were measured by ELISA. The synovial tissues of the joint of all the rats were obtained and NLRP3 inflammasome analysed by Western blot. Results: The results revealed that compared with control rats, 19.2 g/kg dose of ZTD lowered the owestry disability index of the rats significantly from 2.3 ± 0.4 to 0.9 ± 0.3 (p 0.05). Pathomorphology analysis showed that ZTD attenuated the swelling of toes and the infiltration of inflammatory cells in synovium significantly (p 0.05). Further, ZTD decreased the IL-1β (p 0.05) and TNF-α levels (p 0.05) at all doses, and inhibited NLRP3 (p 0.01), caspase-1 (p 0.01), ASC (p 0.01), IL-1β (p 0.01) and IL-18 (p 0.01) protein ex pressions in the lavage fluid of articular cavities in MSU crystal-treated rats. Conclusion: The results indicate that ZTD ameliorates gouty arthritis in rats by inhibiting NLRP3 inflammasome, and thus can potentially be developed into a new drug for the treatment of gouty arthritis.