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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
                           Δ


                 1*
                          2 #
          魏 超 ,于 江 ,盛关云 ,蔡 毅(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
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                                   3
          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)
          中图分类号  R965;R285      文献标志码  A      文章编号  1001-0408(2025)04-0421-06
          DOI  10.6039/j.issn.1001-0408.2025.04.06

          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(collagen Ⅱ)、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,collagen Ⅱ、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。
          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

          Effects  of  jaceosidin  on  inflammatory  injury  in  osteoarthritis  rats  by  regulating  AMPK/NLRP3  signaling
          pathway
                   1
                             2
          WEI Chao ,YU Jiang ,SHENG Guanyun ,CAI Yi(1.  Dept.  of  Pain,  Jianghan  University  Affiliated  Hospital/
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                                               3
          Wuhan  Sixth  Hospital,  Wuhan  430015,  China;2.  Dept.  of  Orthopedic  Surgery,  Jianghan  University  Affiliated
          Hospital/Wuhan  Sixth  Hospital,  Wuhan  430015,  China;3.  Dept.  of  Orthopaedics,  Liuzhou  Hospital  of
          Traditional  Chinese  Medicine,  Guangxi  Liuzhou  545000,  China;4.  Dept.  of  Pain,  Wuhan  Central  Hospital,
          Wuhan 430014, China)

          ABSTRACT   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  collagen  Ⅱ,
          aggrecan (ACAN), and a disintegrin and metalloproteinase with thrombospondin 5 (ADAMTS5), phosphorylated AMPK (p-AMPK),
          AMPK,  NLRP3,  cleaved-caspase-1,  and  cleaved-IL-1β  were  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,
             Δ 基金项目 湖北省自然科学基金项目(No.2022CFB185)               Mankin  score,  the  levels  of  TNF- α,  IL-18  and  IL-6,  and
             *第一作者 主治医师,硕士。研究方向:骨关节疾病基础研究。
                                                             protein  expressions  of ADAMTS5,  NLRP3,  cleaved-caspase-1
          电话:027-82410046。E-mail:beca31@163.com
             # 通信作者 主治医师,硕士。研究方向:骨关节及脊柱疾病基础                  and  cleaved-IL-1β  in  knee  cartilage  were  significantly  decreased
          研究。电话:027-82441142。E-mail:xua9gae@163.com          or  down-regulated.  Protein  expressions  of  collagen  Ⅱ, ACAN


          中国药房  2025年第36卷第4期                                                 China Pharmacy  2025 Vol. 36  No. 4    · 421 ·
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