鸢尾黄素对尿酸钠诱导的小鼠急性痛风性关节炎的保护作用OA

Objective To investigate the protective effect and mechanism of tectorigenin against monosodium urate crystal-induced acute gouty arthritis in mice based on the NLRP3/Caspase-1 signaling pathway.Methods Fifty SPF-grade male C57BL/6 mice were randomly divided into five groups:blank control group,model group,colchicine(30 mg/kg)group,low-dose tectorigenin(20 mg/kg)group,and high-dose tectorigenin(80 mg/kg)group,with 10 mice in each group.The acute gout model was established by plantar injec-tion of 20 μL monosodium urate suspension(25 mg/mL).Mice in colchicine group and tectorigenin groups were pre-treated with the corresponding drugs via intragastric gavage once daily for 3 d before modeling.At 24 h after modeling,the degree of paw swelling was measured,and the pathological morphology was observed;hematoxylin-eosin(HE)staining was used to evaluate tissue damage;enzyme-linked immunosorbent assay(ELISA)was employed to detect serum levels of pro-inflammatory factors(TNF-α,IL-1β,IL-6)and oxidative stress indicators(GSH-Px,SOD,MDA);Western blot was used to determine protein expressions of NLRP3 and Caspase-1 in paw tissue.Results Compared with control group,the paw swelling significantly increased in model group(P<0.01),and the inflammatory cell infiltration in paw tissue increased;serum levels of TNF-α,IL-1β,IL-6,and MDA were significantly up-regulated(P<0.01),while the activities of GSH-Px and SOD significantly decreased(P<0.01);in addition,the protein expressions of NLRP3 and Caspase-1 in paw tissue were significantly up-regulated(P<0.01).Compared with model group,the paw swelling significantly reduced in colchicine group and tectorigenin groups(P<0.01),and the inflammatory cell infiltration in paw tissue markedly decreased;serum levels of TNF-α,IL-1β,IL-6,and MDA were significantly down-regulated(P<0.01),while the activities of GSH-Px and SOD signifi-cantly increased(P<0.01);protein expressions of NLRP3 and Caspase-1 in paw tissue were significantly down-regulated(P<0.01).The improvement effect in high-dose tectorigenin group was better than that in low-dose group and colchicine group.Conclusion Tectorigenin can effectively alleviate the monosodium urate-induced acute gouty arthritis in mice by inhibiting the activation of the NLRP3/Caspase-1 signaling pathway,thereby reducing inflammatory response and oxidative stress damage.