| 胡彬,饶姣雨,江林,等.千金藤素通过抑制TLR4-NLRP3炎症小体及炎症因子治疗痛风性关节炎[J].浙江中医药大学学报,2023,47(12):1374-1382. |
| 千金藤素通过抑制TLR4-NLRP3炎症小体及炎症因子治疗痛风性关节炎 |
| Cepharanthin Alleviate Gouty Arthritis by Inhibiting NLRP3 Inflammasome and Inflammation Factors |
| DOI：10.16466/j.issn1005-5509.2023.12.002 |
| 中文关键词: 痛风 关节炎 NLRP3炎性小体 炎症因子 千金藤素 秋水仙碱 |
| 英文关键词: gout arthritis NLRP3 inflammasome cytokines cepharanthin colchicine |
| 基金项目:广州市民生科技攻关计划项目(201903010087) |
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| 中文摘要: |
| [目的] 评价千金藤素的体内外抗炎效果，探讨其治疗痛风性关节炎的作用机制。[方法]采用噻唑蓝(3-(4，5-Dimethylthiazol-2-yl)-2，5-diphenyltet -razolium bromide，MTT)比色法检测千金藤素对RAW264.7巨噬细胞的活性抑制作用。采用酶联免疫吸附试验(enzyme linked immunosorbent assay，ELISA)检测千金藤素对肿瘤坏死因子-α(tumor necrosis factor-α，TNF-α)、白细胞介素-1β(interleukin-1β，IL-1β)和 IL-6分泌的影响。以免疫印迹法分别检测千金藤素对Toll样受体4(Toll-like receptor 4，TLR4)、髓样分化因子88(myeloid differentiation factor 88，MYD88)、NOD样受体蛋白3(NOD-like receptor protein 3，NLRP3)/凋亡相关微粒蛋白(apoptosis-associated speck-like protein containing a CARD，ASC)/半胱天冬酶-1(caspase-1)炎症小体的蛋白表达的影响。采用尿酸钠诱导SD大鼠关节炎模型，通过炎症指数以及TNF-α、IL-1β和IL-6炎症因子及TLR4-NLRP3相关蛋白的表达，评价千金藤素的体内抗炎作用。[结果] 千金藤素抑制RAW264.7细胞活力的半数抑制浓度(half maximal inhibitory concentration，IC50)为(62.51±5.36) μmol·L-1，弱于秋水仙碱(26.89±5.14) μmol·L-1。在RAW264.7细胞中，1～10 μmol·L-1千金藤素显著抑制尿酸钠晶体诱导的炎症因子TNF-α、IL-1β和IL-6的分泌与mRNA表达，也抑制了尿酸钠晶体诱导的TLR4、MYD88及NLRP3炎性小体的蛋白表达。在关节炎大鼠模型中，1～10 mg·kg-1千金藤素能够剂量依赖性地减轻关节肿胀，并抑制TNF-α、IL-1β和IL-6分泌及TLR4-NLRP3炎症小体的蛋白表达。[结论] 千金藤素可通过抑制炎症因子TNF-α、IL-1β和IL-6的表达，以及抑制尿酸钠介导的TLR4-NLRP3炎症小体的表达，发挥抗关节炎作用。 |
| 英文摘要: |
| [Objective] To evaluate the anti-inflammatory effect of cepharanthin in vitro and in vivo， and to explore its mechanism of action in the treatment of gouty arthritis. [Methods] 3-(4，5-Dimethylthiazol-2-yl)-2，5-diphenyltetrazolium bromide(MTT) assay was used to evaluate the effect of cepharanthin on cell viability in RAW264.7 cells. Enzyme linked immunosorbent assay(ELISA) and Western blot methods were used to detect the effects of cepharanthin on secretion and protein expression of inflammatory factors tumor necrosis factor-α(TNF-α)， interleukin-1β(IL-1β)， interleukin-6(IL-6)， toll-like receptor 4(TLR4)， myeloid differentiation factor 88(MYD88) and NOD-like receptor protein 3(NLRP3)/apoptosis-associated speck-like protein containing a CARD(ASC)/caspase-1 inflammasome in vitro and in vivo. Gouty arthritis model was established by monosodium urate(MSU) stimulation in SD rats. The anti-inflammatory related indexes of cepharanthin were detected. The anti-inflammatory effect of cepharanthin was evaluated by detecting the expression of TNF-α， IL-1β， IL-6 and TLR4-NLRP3 related protein. [Results] The half maximal inhibitory concentration(IC50) of cepharanthin to cell viability in RAW264.7 cells was (62.51±5.36) μmol·L-1， weaker than that of colchicine (26.89±5.14) μmol·L-1. In RAW264.7 cells，1～10 μmol·L-1 cepharanthin significantly inhibited the secretion and mRNA expression of MSU-induced inflammatory factors TNF-α， IL-1β and IL-6， as also protein expression of TLR4-NLRP3 inflammasome. In rats arthritis model，1～10 mg·kg-1 cepharanthin dose-dependently improved toe swelling， and reduced the secretion of inflammatory factors TNF-α， IL-1β and IL-6， and protein expression of TLR4-NLRP3 inflammasome. [Conclusion] Cepharanthin exerts anti-arthritis effects by inhibiting the expression of inflammatory factors TNF-α， IL-1β and IL-6， and the expression of TLR4-NLRP3 inflammasome induced by MSU. |
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