当前位置:
首页
网刊
黄芩苷对尿酸钠诱导RAW264.7细胞NLRP3及炎症因子表达的影响
黄芩苷对尿酸钠诱导RAW264.7细胞NLRP3及炎症因子表达的影响
文学平,刘德俊,裴忆雪,徐凌云

武汉轻工大学生物与制药工程学院,武汉 430023
Effect of baicalin on the expression of NLRP3 inflammsome and inflammatory factors in monosodium urate-induced RAW264.7 macrophages
(School of Biological and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan 430023, China)

摘要参考文献相关文章

起始页:190

摘要:[摘要] 目的:研究黄芩苷对尿酸钠诱导RAW264.7细胞NLRP3炎性小体及炎症因子表达的影响。方法:取RAW264.7细胞分为对照组、模型组和药物组,模型组用尿酸钠(终浓度2 mg?mL-1)刺激,药物组先加入不同浓度黄芩苷(终浓度为2.5,5,10和20 μg?mL-1)预处理1 h后再加入尿酸钠。24 h后收集细胞,用qRT-PCR法检测TNF-α,IL-1β,IL-18和NLRP3的mRNA表达水平;收集细胞培养上清液,用ELISA法检测TNF-α,IL-1β和IL-18的浓度。结果:与对照组比较,模型组巨噬细胞NLRP3及炎症因子TNF-α,IL-1β和IL-18的基因表达显著上调,巨噬细胞分泌TNF-α,IL-1β和IL-18显著增加;与模型组比较,黄芩苷组显著抑制上述指标。结论: NLRP3炎性小体参与尿酸钠诱导的炎性反应,黄芩苷可抑制NLRP3的mRNA表达,减少炎症因子TNF-α,IL-1β和IL-18的分泌而发挥抗炎作用。

关键词:[关键词] 黄芩苷;RAW264.7细胞;尿酸钠;NLRP3炎性小体;IL-1β;IL-18;TNF-α

通讯作者:

基金项目:

作者简介:

Abstract:[Abstract] Objective: To explore the antigout mechanism of baicalin by investigating its effects on the expression of NLRP3 inflammatory and some inflammatory factors in monosodium urate-induced RAW264.7 macrophages. Methods: Cultured murine RAW264.7 macrophages in vitro were divided into control group, experimental drug groups which pre-received different concentrations of baicalin at final concentration of 2.5, 5, 10 or 20 μg?mL-1, respectively for 1 h before being induced by monosodium urate suspension at final concentration of 2 mg?mL-1, and model group which was treated by monosodium urate suspension at final concentration of 2 mg?mL-1. Twenty-four hours later the cells were collected and the mRNA expression of TNF-α, IL-1β, IL-18 and NLRP3 was determined by fluorescence quantitative PCR method and the levels of TNF-α, IL-1β and IL-18 in cell supernatant were detected by ELISA. Results: Compared with the control group, the gene expression of NLRP3, TNF-α, IL-1β and IL-18 was significantly upregulated and the levels of TNF-α, IL-1β and IL-18 were significantly increased by monosodium urate in the model group, and compared with the model group, the gene expression of TNF-α, IL-1β, IL-18 and NLRP3 and their contents were significantly inhibited in the baicalin-treated groups. Conclusion: Monosodium urate activates NLRP3 inflammasome and facilitates the excretion of TNF-α, IL-1β and IL-18, and baicalin can significantly inhibit the phenomenon and has anti-inflammatory effect.

Key words:[Key words] baicalin; murine macrophage RAW264.7; monosodium urate; NLRP3 inflammasome; IL-1β; IL-18; TNF-α

    [1] RICHETTE P, BARDIN T. Gout[J]. Lancet,2010, 375(9711): 318-328.
    [2] MARTINON F, PETRILLI V, MAYOR A, et al. Gout-associated uric acid crystals activate the NALP3 inflammasome[J]. Nature, 2006, 440(7081):237-241.
    [3] QING YF, ZHANG QB, ZHOU JG, et al. Changes in toll-like receptor (TLR)4-NFκB-IL1β signaling in male gout patients might be involved in the pathogenesis of primary gouty arthritis[J]. Rheumatol Int, 2014, 34(2):213-220.
    [4] BUSSO N, SO A. Mechanisms of inflammation in gout[J]. Arthritis Res Ther, 2010, 12(2):206-213. 
    [5] KINGSBURY SR, CONAGHAN PG, MCDERMOTT MF. The role of the NLRP3 inflammasome in gout[J]. J Inflamm Res, 2011, 4:39-49. 
    [6] 李俊杰, 文学平, 徐凌云. 黄芩苷新剂型及其药理学研究进展

    [J]. 中国新药杂志, 2017, 26(17): 2046-2051.
    [7] YE C, LI S, YAO W, et al. The anti-inflammatory effects of baicalin through suppression of NLRP3 inflammasome pathway in LPS-challenged piglet mononuclear phagocytes[J]. Innate Immun, 2016, 22(3):196-204.
    [8] 文学平, 刘德俊, 裴忆雪, 等. 黄芩苷抗急性痛风性关节炎的实验研究

    [J]. 中药材, 2017, 40(8): 1953-1956.
    [9] CHITRA D, SOWMIYA K, MAHABOOBKHAN R. Morin, a bioflavonoid suppresses monosodium urate crystal-induced inflammatory immune response in RAW 264.7 macrophages through the inhibition of inflammatory mediators, intracellular ROS levels and NF-κB Activation[J]. Plos One, 2015, 10(12):e0145093.
    [10] FUKUDA T, TAKEDA S, XU R, et al. Sema3A regulates bone-mass accrual through sensory innervations[J]. Nature, 2013, 497(7450):490-493.
    [11] LIU L, XUE Y, ZHU Y, et al. Interleukin 37 limits monosodium urate crystal-induced innate immune responses in human and murine models of gout[J]. Arthritis Res Ther, 2016, 18(1):268.
    [12] HUGLE T, KRENN V. Histopathophysiology of Gout[J]. Ther Umsch, 2016, 73(3):137-140.
    [13] MARTIN WJ, WALTON M, HARPER J. Resident macrophages initiating and driving inflammation in a monosodium urate monohydrate crystal-induced murine peritoneal model of acute gout[J]. Arthritis Rheum, 2009, 60(1): 281-289.
    [14] MITROULIS I, KAMBAS K, RITIS K. Neutrophils, IL-1β, and gout: is there a link?[J].Semin Immunopathol, 2013, 35(4):501-512.
    [15] DIAZ-TORNE C, PEREZ-HERRERO N, PEREZ-RUIZ F. New medications in development for the treatment of hyperuricemia of gout[J]. Curr Opin Rheumatol, 2015, 27(2): 164-169.
    [16] MCCARTHY M. Enhanced interleukin-1β production of PBMCs from patients with gout after stimulation with Toll-like receptor-2 ligands and urate crystals[J]. Arthritis Res Ther, 2012, 14(4):1-10.
    [17] LUO W, WANG CY, JIN L. Baicalin downregulates Porphyromonas gingivalis lipopolysaccharide-upregulated IL-6 and IL-8 expression in human oral keratinocytes by negative regulation of TLR signaling[J]. PLoS One, 2012, 7(12):e51008.
    [18] FENG A, ZHOU G, YUAN X, et al. Inhibitory effect of baicalin on iNOS and NO expression in intestinal mucosa of rats with acute endotoxemia[J]. PLoS One, 2013, 8(12):e80997. 
    [19] YANG X, YANG J, ZOU H. Baicalin inhibits IL-17-mediated joint inflammation in murine adjuvant-induced arthritis[J]. Clin Dev Immunol, 2013:268065.
    [20] FU S, XU L, LI S, et al. Baicalin suppresses NLRP3 inflammasome and nuclear factor-kappa B (NF-κB) signaling during Haemophilus parasuis infection[J]. Vet Res, 2016, 47(1):80-90.