Abstract：
The aim of this study was to validate the preventive effects of koumine (KM), a monoterpene indole alkaloid, on gouty arthritis (GA) and to explore its possible mechanisms. C57BL/6 mice were intraperitoneally administered KM (0.8, 2.4 or 7.2 mg/kg), colchicine (3.0 mg/kg) or sterile saline. One hour later, a monosodium urate (MSU) suspension was injected into the right hind paws of the mice to establish an acute gout model. Inflammation symptoms were evaluated at 0, 3, 6, 12 and 24 h, and the mechanical withdrawal threshold was evaluated at 0, 6 and 24 h. After 24 h, the mice were euthanized, and the joint tissue, kidney and blood were collected for subsequent experiments. Histological examination and antioxidant enzyme, kidney index and serum uric acid (UA) measurements were taken. The expression levels of the signalling pathway components were determined. KM effectively alleviated the symptoms of redness, swelling and pain; counteracted inflammatory cell infiltration; and increased antioxidant enzyme levels, reduced kidney index and seru UA levels through regulating UA excretion in MSU-induced mice. The expression of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) signalling pathway proteins and mRNA were reduced in the KM group. These results suggest that KM may be effective in alleviating GA through the TLR4/NF-κB/NLRP3 pathway.
摘要：
这项研究的目的是验证koumine(KM)的预防效果，一种单萜吲哚生物碱，痛风性关节炎（GA）并探讨其可能的机制。C57BL/6小鼠腹膜内给药KM（0.8、2.4或7.2mg/kg），秋水仙碱（3.0mg/kg）或无菌盐水。一个小时后,将尿酸单钠（MSU）悬浮液注射到小鼠的右后爪中以建立急性痛风模型。在0、3、6、12和24小时评估炎症症状，并在0、6和24小时评估机械退出阈值。24小时后，对小鼠实施安乐死,和关节组织，收集肾脏和血液用于后续实验。组织学检查和抗氧化酶，进行肾指数和血清尿酸(UA)测量.确定信号传导途径组分的表达水平。KM有效缓解了红肿症状，肿胀和疼痛;抵消炎症细胞浸润;和增加抗氧化酶水平,通过调节MSU诱导小鼠的UA排泄降低肾脏指数和血清UA水平。Toll样受体4(TLR4)/核因子κB(NF-κB)/核苷酸结合寡聚化结构域的表达,在KM组中，富含亮氨酸的重复序列和含pyrin结构域的3（NLRP3）信号通路蛋白和mRNA减少。这些结果表明，KM可能通过TLR4/NF-κB/NLRP3途径有效缓解GA。
