棕矢车菊素调节AMPK/NLRP3信号通路对骨关节炎大鼠炎性损伤的影响  

Effects of jaceosidin on inflammatory injury in osteoarthritis rats by regulating AMPK/NLRP3 signaling pathway

作　　者：魏超 于江 盛关云 蔡毅[4] WEI Chao;YU Jiang;SHENG Guanyun;CAI Yi(Dept.of Pain,Jianghan University Affiliated Hospital/Wuhan Sixth Hospital,Wuhan 430015,China;Dept.of Orthopedic Surgery,Jianghan University Affiliated Hospital/Wuhan Sixth Hospital,Wuhan 430015,China;Dept.of Orthopaedics,Liuzhou Hospital of Traditional Chinese Medicine,Guangxi Liuzhou 545000,China;Dept.of Pain,Wuhan Central Hospital,Wuhan 430014,China)

机构地区：[1]江汉大学附属医院/武汉市第六医院疼痛科,武汉430015 [2]江汉大学附属医院/武汉市第六医院骨外科,武汉430015 [3]柳州市中医医院综合骨科,广西柳州545000 [4]武汉市中心医院疼痛科,武汉430014

出　　处：《中国药房》2025年第4期421-426,共6页China Pharmacy

基　　金：湖北省自然科学基金项目(No.2022CFB185)。

摘　　要：目的探讨棕矢车菊素激活腺苷一磷酸活化的蛋白激酶(AMPK)/NOD样受体蛋白3(NLRP3)信号通路对大鼠骨关节炎(OA)的影响。方法大鼠随机分为OA组、棕矢车菊素(33.33 mg/kg)组、AMPK抑制剂(Compound C,20 mg/kg)组、棕矢车菊素(33.33 mg/kg)+Compound C(20 mg/kg)组和假手术组,每组12只。除假手术组外,其余各组大鼠均通过改良Hulth法建立OA模型。建模成功后,各组大鼠灌胃相应剂量的棕矢车菊素或生理盐水,且腹腔注射相应剂量的Compound C或生理盐水,每天1次,持续8周。末次给药24 h后,检测各组大鼠膝关节肿胀度;观察大鼠膝关节软骨组织的病理并进行Mankin评分;检测大鼠膝关节软骨组织中肿瘤坏死因子α(TNF-α)、白细胞介素18(IL-18)、IL-6水平,胶原蛋白Ⅱ(collagenⅡ)、聚集蛋白聚糖(ACAN)、血小板反应蛋白解整合素金属肽酶5(ADAMTS5)蛋白表达,以及磷酸化AMPK(p-AMPK)、AMPK、NLRP3、裂解的胱天蛋白酶1(cleaved-caspase-1)、裂解的IL-1β(cleaved-IL-1β)蛋白表达。结果与OA组比较,棕矢车菊素组大鼠软骨组织缺损现象有所缓解,软骨基质染色加深,软骨细胞数量增多;膝关节肿胀度、Mankin评分和膝关节软骨组织中TNF-α、IL-18、IL-6水平以及ADAMTS5、NLRP3、cleaved-caspase-1、cleaved-IL-1β蛋白表达水平均显著降低或下调,collagenⅡ、ACAN蛋白表达水平和AMPK磷酸化均显著升高或上调(P<0.05)。Compound C显著逆转了棕矢车菊素对OA大鼠上述指标的改善作用(P<0.05)。结论棕矢车菊素可能通过调控AMPK/NLRP3信号通路来抑制OA大鼠炎症反应及细胞外基质降解。OBJECTIVE To investigate the effects of jaceosidin on osteoarthritis(OA)of rats by regulating adenosine monophosphate-activated protein kinase(AMPK)/NOD-like receptor protein 3(NLRP3)pathway.METHODS Rats were randomly separated into OA group,jaceosidin group(33.33 mg/kg),AMPK inhibitor(Compound C,20 mg/kg)group,jaceosidin(33.33 mg/kg)+Compound C(20 mg/kg)group,and sham operation group,with 12 rats in each group.Except for the sham operation group,the OA model was induced with modified Hulth method in all other groups.After successful modeling,they were given a relevant dose of jaceosidin or normal saline intragastrically,and Compound C or normal saline intraperitoneally,once a day,for consecutive 8 weeks.Twenty-four h after the last medication,the degree of knee joint swelling in rats from each group was measured.The pathological changes of the articular cartilage tissue in the knee joints,and the Mankin score were assessed.The levels of tumor necrosis factor-α(TNF-α),interleukin-18(IL-18),and IL-6,as well as the protein expressions of collagenⅡ,aggrecan(ACAN),and a disintegrin and metalloproteinase with thrombospondin 5(ADAMTS5),phosphorylated AMPK(p-AMPK),AMPK,NLRP3,cleaved-caspase-1,and cleaved-IL-1βwere detected in the articular cartilage tissue of rats’knees.RESULTS Compared with OA group,the cartilage tissue defect of jaceosidin group was relieved,the cartilage matrix staining was deepened,and the number of chondrocytes was increased.Knee swelling,Mankin score,the levels of TNF-α,IL-18 and IL-6,and protein expressions of ADAMTS5,NLRP3,cleaved-caspase-1 and cleaved-IL-1βin knee cartilage were significantly decreased or down-regulated.Protein expressions of collagenⅡ,ACAN and phosphorylation level of AMPK were significantly increased or up-regulated(P<0.05).Compound C significantly reversed the improvement effects of jaceosidin on the above indexes of OA rats(P<0.05).CONCLUSIONS Jaceosidin may inhibit inflammation and extracellular matrix degradation in OA rats by regulating the AMPK/NLRP3 signalin

关 键 词：棕矢车菊素 AMPK/NLRP3信号通路 骨关节炎 炎症 细胞外基质 

分 类 号：R965[医药卫生—药理学] R285[医药卫生—药学]