2022 年第 6 期 第 17 卷

基于Toll样受体4/核因子κB信号通路探讨槲皮素治疗胶原诱导性关节炎模型大鼠的作用机制

Analysis of mechanism of quercetin on collagen-induced arthritis model rats based on Toll-like receptor 4/nuclear factor-κB signaling pathway

作者：刘君1董秋梅2

英文作者：Liu Jun1 Dong Qiumei2

单位：1内蒙古医科大学中医学院，呼和浩特010000；2内蒙古医科大学中医学院中医内科教研室,呼和浩特010000

英文单位：1College of Traditional Chinese Medicine Inner Mongolia Medical University Hohhot 010000 China; 2Department of Internal Medicine of Traditional Chinese Medicine College of Traditional Chinese Medicine Inner Mongolia Medical University Hohhot 010000 China

关键词：类风湿关节炎；胶原诱导性关节炎模型；槲皮素；Toll样受体4/核因子κB信号通路

英文关键词：Rheumatoidarthritis;Collagen-inducedarthritismodel;Quercetin;Toll-likereceptor4/nuclearfactor-κBsignalingpathway

• 摘要：

• 目的 基于Toll样受体4（TLR4）/核因子κB信号通路探讨槲皮素治疗胶原诱导性关节炎（CIA）模型大鼠的作用机制。方法 选取无特定病原体级雄性SD大鼠60只，按随机数字表法将大鼠分为正常对照组、模型组、甲氨蝶呤组和槲皮素组，各15只。CIA造模成功后每组筛选10只用于实验。正常对照组不予造模及药物干预，模型组CIA造模后予与槲皮素组等量的0.9%氯化钠注射液灌胃，甲氨蝶呤组CIA造模后予甲氨蝶呤腹腔注射，槲皮素组CIA造模后予槲皮素灌胃，均连续给药4周。比较各组大鼠后足足掌厚度、关节炎指数（AI）评分、血清细胞因子水平及踝关节滑膜组织细胞因子表达情况。结果 灌胃2、3、4周，甲氨蝶呤组、槲皮素组大鼠足掌厚度均小于模型组，AI评分均低于模型组［AI评分：（6.5±1.2）、（7.6±0.5）分比（8.1±0.6）分，（5.7±1.1）、（6.6±0.5）分比（8.4±0.7）分，（4.6±1.0）、（5.9±0.7）分比（8.5±0.7）分］（均P<0.05）。灌胃结束后，模型组大鼠血清γ-干扰素、白细胞介素1β（IL-1β）、IL-6、IL-17水平，踝关节滑膜组织中IL-1β、IL-6、IL-17、TLR4、核因子κB p50及核因子κB p65蛋白表达强度均高于正常对照组，而甲氨蝶呤组、槲皮素组均低于模型组（均P＜0.05）；甲氨蝶呤组与槲皮素组上述指标比较差异均无统计学意义（均P＞0.05）。结论 槲皮素可有效缓解CIA大鼠关节滑膜炎症,调控细胞因子，抑制TLR4/核因子κB通路,可能是治疗类风湿关节炎的潜在药物。

• Objective To analyze the mechanism of quercetin on collagen-induced arthritis (CIA) model rats based on Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway. Methods Totally 60 specific pathogen free grade male SD rats were enrolled. They were randomly divided into normal control group, model group, methotrexate group and quercetin group, with 15 cases in each group. After successfully CIA modeling, 10 rats in each group were selected for the experiment. The normal control group was not given modeling and drug intervention. After CIA modeling, the model group was given equivalent amount of 0.9% sodium chloride injection gavage as the quercetin group, the methotrexate group was given methotrexate intraperitoneal injection, and the quercetin group was given quercetin gavage. All the groups were treated for 4 weeks. The thickness of hind paw, arthritis index (AI) score, serum levels of cytokines and expression of cytokines in synovial tissue of ankle joint were compared among the groups. Results   Compared with model group, the thicknesses of paw in methotrexate group and quercetin group were less and AI scores were lower in 2, 3 and 4 weeks of gavage ［AI scores: （6.5±1.2）,（7.6±0.5） vs （8.1±0.6）;（5.7±1.1）,（6.6±0.5） vs （8.4±0.7）;（4.6±1.0）,（5.9±0.7） vs （8.5±0.7）］(all P<0.05). After gavage, serum levels of interferon-γ (IFN-γ), interleukin-1β (IL-1β), IL-6 and IL-17, as well as expression levels of IL-1β, IL-6, IL-17, TLR4, NF-κB p50 and NF-κB p65 in synovial tissue of ankle joint in model group were higher than those in normal control group, while the levels in methotrexate group and quercetin group were lower than those in model group (all P<0.05), and there were no significantly differences between methotrexate group and quercetin group (all P>0.05). Conclusions  Quercetin can effectively alleviate synovitis of joint in CIA rats, regulate cytokines and inhibit TLR4/NF-κB signaling pathway. It is a potential drug for the treatment of rheumatoid arthritis.