Study on the protective effect of dimethyl fumarate on acute gouty arthritis in rats and its mechanism

Wang Guozhen; Liu Zijia; Tang Duo; Zhou Zhixiang; Zhang Tie

doi:10.3760/j.issn.1673-4777.2025.04.015

Abstract：Objective To investigate the protective effect of dimethyl fumarate(DMF)on acute gouty arthritis in rats and its mechanism.Methods Twenty-one male SD rats were randomly divided into physiological saline group,urate crystal(MSU)group,and MSU+DMF group after one week of feeding in an environment without specific pathogens,with seven rats in each group.In the physiological saline group,no model was made,and physiological saline was administered by gavage;The model of acute gouty arthritis was made by MSU in MSU group and MSU+DMF group,and the rats were gavaged with physiological saline and DMF respectively.The degree of ankle swelling and gait behavior rating were compared between the groups,and the pathological sections of rat ankle synovium were stained with hematoxylin-eosin.The histopathological changes and inflammatory cell infiltration of rats in each group were observed.The protein expressions of scutellarin D,NOD like receptor protein 3(NLRP3)and caspase-1 in synovial tissue of rats in each group were determined by integrated optical density method.The serum levels of interleukin-1 β(IL-1β),IL-6 and tumor necrosis factor α(TNF-α)were determined by enzyme-linked immunosorbent assay.Results The joint swelling degrees of MSU+DMF group and MSU group were greater than those of normal saline group at 4,8,24 and 48 h after treatment,but the joint swelling degrees of MSU+DMF group were less than those of MSU group(all P＜0.05).At 4,8,24,48 h after treatment,the MSU+DMF group and MSU group had significantly higher gait behavior rating than the physiological group,but the MSU+DMF group had significantly lower gait behavior rating than the MSU group(all P＜0.05).The MSU group had a large number of inflammatory cell infiltration and obvious inflammatory response.Compared with the MSU group,the MSU+DMF group had less inflammatory response,less inflammatory cell infiltration,and more uniform distribution of synovial cells.The protein expression of NLRP3,caspase-1,and gasdermin D and the levels of IL-1β,IL-6,and TNF-α in the synovial tissue of the MSU group were significantly higher than those in the physiological saline group,and those in the MSU+DMF group were significantly lower than those in the MSU group[inflammatory factors:(64±7)ng/L vs(106±13)ng/L,(27±4)ng/L vs(59±8)ng/L,(11.3±1.5)ng/L vs(27.8±3.9)ng/L](all P＜0.05).Conclusions DMF has a protective effect on MSU induced acute gouty arthritis in rats,which may be related to the inhibition of NLRP3 inflammasome and NLRP3 inflammatory pathway.