异落新妇苷通过调节NLRP3炎症小体和NF-κB信号通路减轻尿酸钠诱导的小鼠急性痛风性关节炎机制研究  

Mechanism Study of Isoastilbin on Attenuating MSU-Induced Acute Gouty Arthritis in Mice Through Modulating NLRP3 Inflammasome and NF-κB Signaling Pathway

作　　者：姚燕箐 汪焱 徐文静 吴晨曦 楚秉泉 夏道宗[1] YAO Yanjing;WANG Yan;XU Wenjing(School of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou 310053,China)

机构地区：[1]浙江中医药大学药学院,杭州310053

出　　处：《浙江中医药大学学报》2022年第9期929-935,944,共8页Journal of Zhejiang Chinese Medical University

基　　金：国家自然科学基金项目(82074085,81673656);浙江省自然科学基金项目(LY21H280006);浙江中医药大学省重点建设高校优势特色学科(中药学)开放基金重点项目(ZYAOXZD2019002)。

摘　　要：[目的]基于NOD样受体蛋白3(NOD-like receptor pyrin domain 3,NLRP3)炎症小体和核因子-κB(nuclear factor-κB,NF-κB)信号通路,研究异落新妇苷(isoastilbin,IA)对小鼠急性痛风性关节炎模型的抗炎作用及机制。[方法]通过关节腔注射尿酸钠(monosodium urate,MSU)混悬液,建立小鼠急性痛风性关节炎模型,以自制足趾容积测量装置测定踝关节肿胀度;苏木精-伊红(hematoxylin-eosin,HE)染色法观察踝关节炎性浸润情况;酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测踝关节中白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的水平;免疫印迹法检测踝关节中NLRP3炎症小体和NF-κB信号通路中相关蛋白的表达情况。[结果]踝关节注射MSU混悬液诱导小鼠产生急性痛风性关节炎。与正常组比较,模型组小鼠踝关节肿胀率明显升高(P<0.01),炎性浸润增加,IL-1β、IL-6、TNF-α分泌水平显著增高(P<0.01),NLRP3炎症小体和NF-κB信号通路相关蛋白表达增加(P<0.01)。与模型组比较,IA具有较强的抗炎效果,剂量依赖性地降低小鼠踝关节肿胀率(P<0.05,P<0.01),减轻炎性浸润情况,减少相关炎症因子的分泌(P<0.01),下调NLRP3炎症小体和NF-κB信号通路相关蛋白表达(P<0.01)。[结论] IA对小鼠急性痛风性关节炎模型表现出较强的抗炎效果,其机制与调节NLRP3炎症小体和NF-κB信号通路相关。[Objective] To study the anti-inflammatory effect and mechanism of isoastilbin(IA) on acute gouty arthritis in mice based on NOD-like receptor pyrin domain 3(NLRP3) inflammasome and nuclear factor-κB(NF-κB) signaling pathway. [Methods] The acute gouty arthritis model in mice was established by injecting monosodium urate(MSU) suspension into the articular cavity. Ankle swelling rate was measured by self-made toe volume installation;the state of inflammatory infiltration within ankle was observed through hematoxylin-eosin(HE) staining;the level of interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α) secreted from ankle was determined by enzyme linked immunosorbent assay(ELISA);the expression of protein in ankle linked to NLRP3 inflammasome and NF-κB signaling pathway was detected by Western blot. [Results] MSU suspension was injected into ankle induced acute gouty arthritis in mice. Compared with normal group, the swelling rate of ankle in model group was significantly increased(P<0.01), inflammatory infiltration was increased,the secretion level of IL-1β, IL-6 and TNF-α was significantly increased(P<0.01), and the expression of NLRP3 inflammasome and NF-κB signaling pathway related proteins were increased(P <0.01). Compared with model group, IA had a good anti-inflammatory effect. IA reduced the swelling rate of ankle in a dose-dependent manner(P <0.05, P <0.01), alleviated inflammatory infiltration, reduced the secretion of related inflammatory cytokines(P<0.01), and down-regulated the expression of NLRP3 inflammasome and NF-κB signaling pathway related proteins(P<0.01). [Conclusion] IA has a strong anti-inflammatory effect in mice on acute gouty arthritis, and its mechanism is related to the regulation of NLRP3 inflammasome and NF-κB signaling pathway.

关 键 词：异落新妇苷 急性痛风性关节炎 尿酸钠 踝关节肿胀 炎症因子 NLRP3炎症小体 NF-ΚB信号通路 机制研究 

分 类 号：R331[医药卫生—人体生理学]