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基于 FOXO3/Sirt1 通路探讨槲皮素对腰椎间盘突出症大鼠椎间

          盘退变的影响
                               Δ


          肖博文 ,彭 聪,张森伟(荆州市中心医院疼痛科,湖北 荆州 434000)
                *

          中图分类号  R285;R965      文献标志码  A      文章编号  1001-0408(2026)01-0049-06
          DOI  10.6039/j.issn.1001-0408.2026.01.09

          摘  要  目的  研究槲皮素(QUE)对腰椎间盘突出症(LDH)大鼠椎间盘退变的影响,并基于叉头框蛋白O3/沉默信息调节因子1
         (FOXO3/Sirt1)通路探讨其作用机制。方法  构建LDH大鼠模型,将造模成功的大鼠随机分为LDH组(灌胃+腹腔注射等体积生
          理盐水)、QUE-L组(灌胃50 mg/kg的QUE+腹腔注射等体积生理盐水)、QUE-H组(灌胃100 mg/kg的QUE+腹腔注射等体积生理
          盐水)、QUE-H+EX-527(Sirt1抑制剂)组(灌胃100 mg/kg的QUE+腹腔注射1 mg/kg的EX-527溶液),每组12只;另取12只正常健
          康大鼠作为Control组(灌胃+腹腔注射等体积生理盐水)。每天给药1次,连续8周。末次给药后,检测大鼠疼痛阈值、血清中炎症
          因子水平,观察大鼠椎间盘组织病理损伤,检测大鼠椎间盘组织髓核细胞凋亡情况,检测大鼠椎间盘组织中基质金属蛋白酶 3
         (MMP-3)、磷脂酶A2(PLA2)以及凋亡、FOXO3/Sirt1通路相关蛋白表达。结果  与LDH组比较,QUE-L组、QUE-H组大鼠椎间盘
          组织病理损伤显著改善;机械缩足反射阈值、热刺激缩足反射潜伏期,血清中转化生长因子β1、白细胞介素10(IL-10)水平,椎间盘
          组织中B细胞淋巴瘤2(Bcl-2)、FOXO3、Sirt1蛋白的相对表达量均显著升高/延长(P<0.05);血清中肿瘤坏死因子α、IL-1β水平,
          椎间盘组织病理评分,髓核细胞凋亡率,椎间盘组织中MMP-3、PLA2的阳性表达率和Bcl-2相关X蛋白的相对表达量均显著降低
         (P<0.05);与 QUE-H 组比较,QUE-H+EX-527 组大鼠椎间盘组织病理损伤加重,以上指标的变化趋势均发生了显著逆转(P<
          0.05)。结论  QUE可改善LDH大鼠椎间盘退变,其机制可能与激活FOXO3/Sirt1通路有关。
          关键词  槲皮素;腰椎间盘突出症;叉头框蛋白O3;沉默信息调节因子1;凋亡

          Exploration  of  the  effects  of  quercetin  on  intervertebral  disc  degeneration  in  lumbar  intervertebral  disc
          herniation rats based on the FOXO3/Sirt1 pathway
          XIAO Bowen,PENG Cong,ZHANG Senwei(Dept.  of  Pain  Medicine,  Jingzhou  Central  Hospital,  Hubei
          Jingzhou 434000, China)


          ABSTRACT   OBJECTIVE To  investigate  the  effects  of  quercetin (QUE)  on  intervertebral  disc  degeneration  in  rats  with  lumbar
          intervertebral disc herniation (LDH) and explore its mechanism based on the forkhead box protein O3/silent information regulator 1
         (FOXO3/Sirt1)  pathway.  METHODS  A  rat  model  of  LDH  was  established. The  successfully  modeled  rats  were  randomly  divided
          into LDH group (gavaged with and intraperitoneally injected with an equal volume of normal saline), QUE-L group (gavaged with
          50 mg/kg QUE+intraperitoneally injected with an equal volume of normal saline), QUE-H group (gavaged with 100 mg/kg QUE+
          intraperitoneally  injected  with  an  equal  volume  of  normal  saline),  and  QUE-H+EX-527 (a  Sirt1  inhibitor)  group (gavaged  with
          100 mg/kg QUE+intraperitoneally injected with 1 mg/kg EX-527), with 12 rats in each group. Additionally, 12 healthy normal rats
          were  selected  as  the  control  group (gavaged  with  and  intraperitoneally  injected  with  an  equal  volume  of  normal  saline). All  rats
          were  administered  the  corresponding  agents  once  daily  for  consecutive  8  weeks. After  the  final  administration,  the  pain  threshold
          and  serum  levels  of  inflammatory  factors  in  rats  were  measured;  pathological  damage  of  lumbar  intervertebral  disc  tissue  was
          observed,  the  apoptosis  of  nucleus  pulposus  cells  in  lumbar  intervertebral  disc  tissue  was  assessed,  and  the  expression  levels  of
          matrix metalloproteinase-3 (MMP-3), phospholipase A2 (PLA2), as well as apoptosis-related proteins and FOXO3/Sirt1 pathway-
          related  proteins  in  intervertebral  disc  tissue  were  determined.  RESULTS  Compared  with  LDH  group,  pathological  damage  of
          intervertebral  disc  tissue  were  improved  significantly  in  QUE-L  group  and  QUE-H  group;  paw  withdrawal  mechanical  threshold,
          paw  withdrawal  thermal  latency,  the  serum  levels  of  transforming  growth  factor- β1  and  interleukin-10 (IL-10)  as  well  as  the
          expression  levels  of  B-cell  lymphoma-2 (Bcl-2),  FOXO3  and  Sirt1  were  significantly  increased  or  prolonged (P<0.05).  Serum
          levels of tumor necrosis factor-α and IL-1β, histopathological score of intervertebral disc tissue, apoptotic rate of nucleus pulposus
          cells,  positive  expressions  of  MMP-3  and  PLA2  in  intervertebral  disc  tissue  and  expression  levels  of  Bcl-2  associated  X  protein
          were  significantly  decreased (P<0.05).  Compared  with  the  QUE-H  group,  the  QUE-H+EX-527  group  presented  aggravated
                                                             pathological  damage  of  intervertebral  disc  tissue,  and  the
             Δ 基金项目 2024年度荆州市科技计划项目(No.2024HD08)
             *第一作者 主治医师,硕士。研究方向:脊柱退变。E-mail:                 trends  of  all  the  above  indicators  were  significantly  reversed
          zvrpnd@163.com                                    (P<0.05).  CONCLUSIONS  QUE  can  ameliorate  intervertebral


          中国药房  2026年第37卷第1期                                                  China Pharmacy  2026 Vol. 37  No. 1    · 49 ·
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