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雷公藤多苷调控 HIF-1α/miR-155-5p/Nrf2 通路改善大鼠肾病综

          合征的机制研究
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          陶伊璠    1, 2* ,宋纯东  1, 2 # ,王 旭 ,张 冲 ,苏 颖 ,郏溪栋 ,姜浩然 (1.河南中医药大学第一附属医院
                                                                             1, 2
          儿科医院肾病紫癜二病区,郑州 450000;2.河南中医药大学儿科医学院,郑州 450046)
          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2026)05-0602-05
          DOI  10.6039/j.issn.1001-0408.2026.05.09

          摘   要  目的  研究雷公藤多苷(TWM)对大鼠肾病综合征的改善作用机制。方法  采用尾静脉注射阿霉素的方法复制肾病综合
          征模型大鼠。将造模成功的大鼠随机分为模型组(蒸馏水)、泼尼松组(10 mg/kg)和TWM高、低剂量组(10、5 mg/kg),另设置不造
          模的空白组(蒸馏水),每组9只。各组大鼠灌胃相应药液/蒸馏水,每天1次,连续6周。观察大鼠肾组织病理学形态;检测大鼠24
          h尿蛋白(24 h-UTP)和血清中生化指标[白蛋白(ALB)、血尿素氮(BUN)、肌酐(SCr)、总胆固醇(CHOL)、甘油三酯(TG)]水平;检
          测大鼠肾组织中氧化应激指标[超氧化物歧化酶(SOD)、丙二醛(MDA)]水平;检测大鼠肾组织中缺氧诱导因子1α(HIF-1α)/微小
          RNA-155-5p(miR-155-5p)/核因子E2相关因子2(Nrf2)信号通路相关mRNA和蛋白表达水平。结果  与空白组比较,模型组大鼠肾
          组织结构紊乱,肾小球少量坏死,肾小管上皮细胞水肿;24 h-UTP,血清中SCr、BUN、CHOL、TG水平,肾组织中MDA水平,肾组织
          中HIF-1α、Kelch样ECH相关蛋白1(Keap1)mRNA和蛋白表达水平以及miR-155-5p表达水平均显著升高(P<0.05);血清中ALB
          水平、肾组织中SOD水平以及Nrf2 mRNA和蛋白表达水平均显著降低(P<0.05)。与模型组比较,TWM高、低剂量组大鼠肾损伤
          明显改善,上述定量指标水平均显著逆转(P<0.05)。结论  TWM可通过调控HIF-1α/miR-155-5p/Nrf2信号通路,减轻氧化应激损
          伤,从而改善大鼠肾病综合征。
          关键词  雷公藤多苷;肾病综合征;氧化应激;HIF-1α/miR-155-5p/Nrf2信号通路

          Mechanistic  study  of Tripterygium  wilfordii  multiglucoside  in  improving  nephrotic  syndrome  via  regulating
          the HIF-1α/miR-155-5p/Nrf2 pathway
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          TAO Yifan ,SONG Chundong ,WANG Xu ,ZHANG Chong ,SU Ying ,JIA Xidong ,JIANG Haoran                1, 2
         (1.  Second Ward  of  Nephropathy  Purpura,  Pediatric  Hospital,  the  First Affiliated  Hospital  of  Henan  University
          of  Chinese  Medicine,  Zhengzhou  450000,  China;2.  School  of  Pediatrics,  Henan  University  of  Chinese
          Medicine, Zhengzhou 450046, China)
          ABSTRACT    OBJECTIVE To study the improvement effect and mechanism of Tripterygium wilfordii multiglucoside (TWM) on
          nephrotic syndrome in rats. METHODS  The nephrotic syndrome model was established by intravenous injection of adriamycin via
          the tail vein. The modeling rats were randomly divided into the model group (distilled water), prednisone group (10 mg/kg), and
          TWM  high-  and  low-dose  groups (10  and  5  mg/kg,  respectively).  Additionally,  blank  group (distilled  water)  without  model
          induction was established. Each group consisted of 9 rats. Rats in each group were administered the corresponding drugs or distilled
          water  by  gavage,  once  a  day,  for  6  consecutive  weeks. The  histopathological  morphology  of  kidney  tissues  in  rats  was  observed;
          the levels of 24-hour urinary protein (24 h-UTP) and serum biochemical indicators [albumin (ALB), blood urea nitrogen (BUN),
          serum  creatinine (SCr),  cholesterol (CHOL),  and  triglyceride (TG)]  in  rats  were  determined;  the  levels  of  oxidative  stress
          indicators  [superoxide  dismutase (SOD),  malondialdehyde (MDA)]  in  kidney  tissue  of  rats  were  determined;  expressions  of
                                                              hypoxia-inducible   factor-1α   (HIF-1α)/microRNA-155-5p
              Δ 基金项目 国家自然科学基金面上项目(No.82074493);河南省           (miR-155-5p)/nuclear  factor  erythriod  2-  related  factor  2
          卫 生 健 康 委 员 会 河 南 省 中 医 药 科 学 研 究 专 项 重 点 课 题(No.  (Nrf2)  signaling  pathway-related  mRNA  and  protein  in  the
          2024ZY1002);河南省卫生健康委员会国家中医药传承创新中心联合                 renal  tissues  of  rats  were  detected.  RESULTS  Compared  with
          共建科研专项立项(No.2024ZXZX1019);河南中医药大学“仲景三名
                                                              the  blank  group,  the  rats  in  the  model  group  exhibited
          人才工程”仲景领军名医项目(No.河中医政〔2025〕116号)                    disordered  renal  tissue  structure,  with  a  small  amount  of
             *第一作者 硕士研究生。研究方向:儿童肾脏病及风湿免疫性疾
                                                              glomerular  necrosis  and  edema  of  the  renal  tubular  epithelial
          病。E-mail:t17518874849@163.com
              # 通信作者 教授,主任医师,博士生导师,博士。研究方向:儿童                 cells. 24 h-UTP, serum levels of SCr, BUN, CHOL and TG,
          肾脏病及风湿免疫性疾病。E-mail:scd670918@126.com                MDA  content,  mRNA  and  protein  expressions  of  HIF-1α  and


          · 602 ·    China Pharmacy  2026 Vol. 37  No. 5                               中国药房  2026年第37卷第5期
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