基于 NLRP3 炎性体轴探讨土茯苓总黄酮对痛风性关节炎的作用和机制  

Effect and Mechanism of Total Flavonoids from Smilacis Glabrae Rhizoma in Treatment of Gouty Arthritis Based on NLRP3 Inflammasomes Axis

作　　者：金晓敏[1] 张晓熙 郭璐 李杨蕾 邢梦雨 田崇梅 夏道宗[1] 

机构地区：[1]浙江中医药大学药学院

出　　处：《中国实验方剂学杂志》2018年第4期90-95,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81673656,81102861,81374048);浙江省中医药科技计划项目(2015ZA062)

摘　　要：目的：研究土茯苓总黄酮（TFSG）对急性痛风性关节炎小鼠的抗炎作用,并初步探讨其作用机制。方法：将90只雄性C57BL/6小鼠随机分为正常组,模型组,秋水仙碱组（0.65 mg·kg^-1）,土茯苓总黄酮低、中、高剂量组（100,300,500 mg·kg^-1）,每组15只。除正常组外,其余各组采用尿酸钠结晶复制小鼠痛风性关节炎模型,测定小鼠踝关节肿胀度;酶联免疫吸附法（ELISA）检测不同组别滑膜组织中白细胞介素-1β（IL-1β）,IL-6,肿瘤坏死因子-α（TNF-α）水平,蛋白免疫印迹法（Western blot）测定滑膜组织中核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）,凋亡相关斑点样蛋白（ASC）,半胱氨酸天冬氨酸蛋白酶-1（Caspase-1）的蛋白表达,实时荧光定量PCR（Real-time PCR）检测NLRP3,ASC,Caspase-1 mRNA水平的表达。结果：与正常组比较,模型组小鼠踝关节肿胀度明显增加（P〈0.01）,模型组小鼠滑膜组织中IL-1β,IL-6,TNF-α水平显著升高（P〈0.01）,NLRP3,ASC,Caspase-1蛋白表达和mRNA水平显著升高（P〈0.01）;与模型组比较,土茯苓总黄酮组能够显著降低小鼠踝关节肿胀度（P〈0.01）,滑膜组织中IL-1β,IL-6,TNF-α水平以及NLRP3,ASC,Caspase-1蛋白水平和mRNA水平显著降低（P〈0.01）。结论：土茯苓总黄酮具有一定的抗痛风性关节炎作用,其作用机制与NLRP3炎性体轴有关。Objective： To observe the anti-inflammatory effect of total flavonoids from Smilacis Glabrae Rhizoma（TFSG） on acute gouty arthritis and its mechanism.Method： Totally 90 C57 BL/6 mice were randomly divided into the normal group,the model group,the colchicine group（0.65 mg·kg^-1）,and the TFSG group（100,300,500 mg·kg^-1）,with 15 mice in each group.The acute gouty arthritis model was induced with monosodium urate（MSU） crystals,except for the normal group,and the mice＇s ankle swelling degree was measured.The mice＇s synovium tissues were collected to detect the inflammatory mediators interleukin-1β（IL-1β）,IL-6 and tumor necrosis factor-α（TNF-α） by enzyme-linked immunosorbent assay.The protein expressions of Nod-like receptor protein 3（NLRP3）,apoptosis-associated speck-like protein（ASC）,and cysteine aspartic acid protease-1（Caspase-1） were detected by Western blot,and the mRNA expressions of NLRP3,ASC,and Caspase-1 messenger in synovium tissues were detected by Real-time PCR.Result： Compared with the normal group,mice ankle swelling degree of the model group increased significantly（P〈0.01）,and the levels of IL-1β,IL-6,TNF-α and the protein and mRNA expressions of NLRP3,ASC and Caspase-1 were significantly increased（P〈0.01）.Compared with the model group,the TFSG group could significantly reduce ankle swelling degree and IL-1β,IL-6 and TNF-α levels（P〈0.01）,as well as NLRP3,ASC,Caspase-1 protein and mRNA expressions（P〈0.01）.Conclusion： TFSG has an anti-gouty arthritis effect,and its mechanism is correlated with NLRP3 inflammasome axis.

关 键 词：土茯苓总黄酮 急性痛风性关节炎 核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎性体轴 

分 类 号：R22[医药卫生—中医基础理论] R285.5[医药卫生—中医学]