文献类型：期刊文献

中文题名：基于TLR4/Myd88/NF-κB信号通路探讨清热散浊饮治疗高尿酸血症合并痛风性关节炎的作用机制

英文题名：Qingre sanzhuo decoction treats hyperuricemia complicated with gouty arthritis via TLR4/Myd88/NF-κB signaling pathway

作者：程伟刚[1];李浩林[1];杨娟娟[1];柏倩[1];景骆羊[1];胡乐乐[2];金芳梅[2];王海东[2]

第一作者：程伟刚

机构：[1]甘肃中医药大学,甘肃兰州730000;[2]甘肃省中医院风湿骨病中心,甘肃兰州730050

第一机构：甘肃中医药大学

年份：2025

卷号：30

期号：4

起止页码：456

中文期刊名：中国临床药理学与治疗学

外文期刊名：Chinese Journal of Clinical Pharmacology and Therapeutics

收录：;北大核心:【北大核心2023】；

基金：国家中医药管理局高水平重点学科建设项目(国中医人教函[2023]85号);甘肃省中医药项目(GZKP-2022-17)。

语种：中文

中文关键词：清热散浊饮;高尿酸血症;痛风性关节炎;Toll样受体4(TLR4)/髓样分化因子88(Myd88)/核因子-κB(NF-κB)

外文关键词：Qingre sanzhuo decoction;hyperuricemia;goutyarthritis;TLR4/Myd88/NF-κB signaling pathway

摘要：目的:探究清热散浊饮对高尿酸血症合并痛风性关节炎大鼠的治疗作用及对TLR4/Myd88/NF-κB信号通路的影响。方法:将48只SD雄性大鼠随机分为空白组、模型组、秋水仙碱组(0.3 mg·kg^(-1)·d^(-1)),清热散浊饮低、中、高剂量组(7.42、14.85、29.70 g·kg^(-1)·d^(-1)),通过酵母膏联合氧嗪酸钾灌胃致高尿酸血症,结合改良后Coderre法致急性痛风性关节炎构建复合大鼠模型。经过7 d干预,测量大鼠右踝关节周径并计算踝关节肿胀度,生化法测定大鼠血尿酸(HUA)水平,HE染色检查大鼠踝关节滑膜组织病理形态改变,酶联免疫吸附法(ELISA)检测大鼠血清中炎症因子、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)水平,蛋白免疫印迹法(Western blot)测定大鼠踝关节滑膜组织中Toll样受体4(TLR4)、髓样分化因子88(Myd88)、核因子-κB(NF-κB)蛋白表达水平,实时荧光定量聚合酶链式反应(Real-time PCR)测定大鼠TLR4、Myd88、NF-κB mRNA表达。结果:与空白组相比,模型组大鼠踝关节肿胀度明显降低(P<0.01),HUA水平增加,滑膜组织结构紊乱,大量炎性细胞浸润,血清中TNF-α、IL-6、IL-1β水平显著升高(P<0.01),踝关节滑膜中TLR4、Myd88、NF-κB蛋白及mRNA表达水平显著上升(P<0.01)。与模型组相比,秋水仙碱组、清热散浊饮中、高剂量组关节肿胀度显著降低(P<0.05),各治疗组滑膜增生及炎症细胞浸润均改善,各给药组HUA及TNF-α、IL-6、IL-1β水平均显著降低(P<0.05,P<0.01),清热散浊饮中、高剂量组能显著降低TLR4、Myd88、NF-κB蛋白及mRNA表达(P<0.01)。结论:清热散浊饮通过抑制TLR4/Myd88/NF-κB通路减少炎症因子释放,在高尿酸血症合并痛风性关节炎的治疗中发挥作用。
AIM:To investigate the therapeutic effect of Qingre sanzhuo decoction on rats with hyperuricaemia combined with gouty arthritis and its effect on TLR4/Myd88/NF-κB signalling pathway.METHODS:Forty-eight SD male rats were randomly divided into blank,model,and colchicine groups(0.3 mg·kg^(-1)·d^(-1)),and Origre sanzhou decotion low,medium and highdosage groups(7.42,14.85,29.70 g·kg^(-1)·d^(-1)),which were treated with the modified Coderre method for hyperuricemia combined with acute gouty arthritis via gavage of yeast paste combined with potassium oxalate,which was used for the treatment of acute gouty arthritis combined with hyperuricemia.A composite rat model of acute gouty arthritis was constructed by combining yeast paste with potassium oxalate gavage to cause hyperuricaemia,combined with the modified Coderre method.After 7 days of intervention,the circumference of the right ankle joint of rats was measured and the swelling of the ankle joint was calculated,the blood uric acid(HUA)level of rats was determined by biochemical method,the histopathological and morphological changes of the synovial membrane of the ankle joint of rats were examined by HE staining,and the serum levels of inflammatory factors,tumour necrosis factor-alpha(TNF-α),interleukin6(IL-6),and IL-1βwere determined by enzyme linked immunosorbent assay(ELISA),and Western blotting was performed to determine the levels of inflammatory factors,TNF-α,and IL-1β.The protein expression levels of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(Myd88),and nuclear factorκB(NF-κB)in the synovial tissues of the ankle joints of the rats were determined by Western blot method,and the mRNA expression of TLR4,Myd88,and NF-κB in the rat was determined by real-time fluorescence quantitative polymerase chain reaction(Real-time PCR).RESULTS:Compared with the blank group,rats in the model group showed significantly lower ankle joint swelling(P<0.01),increased levels of HUA,disorganised synovial tissue structure,large number of inflammatory cells infiltration,and significantly higher serumlevels of TNF-α,IL-6,and IL-1β(P<0.01),and the protein and mRNA expression levels of TLR4,Myd88,and NF-κB in the synovialmembrane of the ankle joints of the model group were significantly increased(P<0.01).levels were significantly increased(P<0.01);compared with the model group,joint swelling was significantly reduced in the colchicine group,and the medium-and high-dose groups of Qingre sanzhuo decoction(P<0.05);synovial hyperplasia and inflammatory cell infiltration were improved in the colchicine group and the medium-and high-dose groups of Qingre sanzhuo decoction,and the HUA and the levels of TNF-α,IL-6,and IL-1βwere significantly decreased in the dosing groups(P<0.05,P<0.01),and compared with the model group,the medium-and high-dose groups of Qingre sanzhuo decoction could significantly reduce the expression of TLR4,Myd88,and NF-κB protein and mRNA(P<0.01).CONCLUSION:Qingre sanzhuo decoction reduces the release of inflammatory factors by inhibiting the TLR4/Myd88/NF-κB pathway,and plays a role in the treatment of hyperuricaemia combined with gouty arthritis.