补阳还五汤对胶原诱导性关节炎小鼠软骨细胞NLRP3/Caspase-1/GSDMD通路和细胞焦亡的影响OA
Effects of Buyang Huanwu Decoction on NLRP3/Caspase-1/GSDMD Pathway and Pyrop-tosis in Chondrocytes of Collagen-Induced Arthritis Mice
目的 研究补阳还五汤(Buyang Huanwu decoction,BHD)对胶原诱导性关节炎(collagen-induced arthritis,CIA)小鼠的治疗作用,探讨 BHD 改善类风湿关节炎(rheumatoid arthritis,RA)的机制.方法 40 只雄性小鼠,随机取10 只作为空白组,另外30 只采用经典 CIA 法诱导小鼠 RA 模型后,随机分为模型组、甲氨蝶呤(methotrexate,MTX)组、BHD 组,每组 10 只,持续治疗 4 w.定期评估踝关节肿胀程度、关节炎指数,治疗结束后观察踝关节病理改变情况,检测血清生化相关指标、踝关节软骨组织中(NOD-like receptor family pyrin domain containing 3,NLRP3)、半胱氨酸天冬氨酸蛋白酶-1(cysteine-1 aspartic acid protease-1,Caspase-1)和焦孔素 D(gasdermin D,GSDMD)蛋白及 mRNA 的表达.结果 与空白组比较,模型组小鼠踝关节滑膜细胞增生,炎性细胞明显浸润,踝关节肿胀度、关节炎指数、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-8(interleukin-8,IL-8)和白细胞介素-1β(interleukin-1β,IL-1β)水平均明显升高(P<0.01),踝关节软骨组织 NLRP3、Caspase-1 及 GSDMD 的蛋白与 mRNA 表达均显著上调(P<0.01);与模型组相比,MTX 组和 BHD 组小鼠踝关节软骨破损、滑膜增生改善,炎性细胞浸润明显减少,踝关节肿胀度、关节炎指数、TNF-α、IL-1β 及 IL-8 水平均显著下降(P<0.01),踝关节软骨组织 NLRP3、Caspase-1 及 GSDMD 蛋白与 mRNA 表达均显著下调(P<0.01).结论 BHD 能有效缓解 CIA 模型小鼠的关节炎症状并抑制其炎症反应,其机制可能与调控 NLRP3/Caspase-1/GSDMD 信号通路,抑制该通路介导的细胞焦亡实现.
Objective To investigate the therapeutic effect of Buyang Huanwu decoction(BHD)on collagen-induced arthritis(CIA)mice,and explore the mechanism by which BHD ameliorates rheumatoid arthritis(RA).Methods Among forty male mice,10 were randomly taken as a blank group,while the rest 30 mice were evenly divided into a model,a methotrexate group and a BHD group by using the classical CIA method to establish RA models.After 4 week's intervention,the ankle swelling degree and arthritis index were assessed regularly.After the treatment,pathological changes of ankle joints were observed,and serum biochemical pa-rameters as well as the protein and mRNA expression of NOD-like receptor family pyrin domain containing 3,NLRP3(NLRP3),cysteine-aspartic acid protease-1(Caspase-1)and Gasdermin D(GSDMD)in ankle car-tilage tissues were detected.Results Compared with the blank control group,the model group exhibited signifi-cantly increased ankle swelling in mouse ankle joints.The ankle swelling score,arthritis index,serum levels of tumor necrosis factor-α(TNF-α),interleukin-8(IL-8)and interleukin-1β(IL-1β)were all markedly ele-vated(P<0.01).Meanwhile,the protein and mRNA expression of NLRP3,Caspase-1 and GSDMD in ankle cartilage tissues were significantly upregulated(P<0.01).In contrast to the model group,both the MTX group and BHD group showed alleviated ankle cartilage damage and synovial hyperplasia,accompanied by evidently reduced inflammatory infiltration.Their ankle swelling score,arthritis index,as well as serum TNF-α,IL-1β and IL-8 concentrations decreased remarkably(P<0.01).Furthermore,the protein and mRNA expression of NLRP3,Caspase-1 and GSDMD in ankle cartilage tissues were significantly downregulated(P<0.01).Con-clusion BHD can effectively alleviate arthritis symptoms and suppresses inflammatory responses in CIA model mice.The mechanism may be related to the regulation of the NLRP3/Caspase-1/GSDMD signaling pathway,thereby inhibiting pyroptosis mediated by this pathway.
冯文龙;陈利锋;杨冰芯
湖北医药学院中部战区总医院 研究生培养基地,湖北 十堰 442000湖北医药学院中部战区总医院 研究生培养基地,湖北 十堰 442000||中部战区总医院 风湿免疫科,湖北 武汉 430070武汉科技大学医学部 医学院,湖北 武汉 430065
医药卫生
补阳还五汤类风湿关节炎细胞焦亡NLRP3/Caspase-1/GSDMD信号通路
Buyang Huanwu decoctionrheumatoid arthritiscellular pyroptosisNLRP3/Caspase-1/GS-DMD signaling pathway
《贵州中医药大学学报》 2026 (4)
55-62,8
武汉市三甲医院院内项目(1683).
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