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芍药苷对溃疡性结肠炎小鼠氧化应激的影响及机制
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          代 鑫 ,王 莹 ,任鑫悦 ,范丁兴 ,李贤哲 ,冯嘉轩 ,娄石磊 ,阎 慧 ,孙 聪 (1.长春中医药大学药学院,
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          长春 130117;2.长春中医药大学临床医学院,长春 130117)
          中图分类号  R965;R285.5      文献标志码  A      文章编号  1001-0408(2025)04-0427-07
          DOI  10.6039/j.issn.1001-0408.2025.04.07
          摘  要  目的  基于腺苷一磷酸活化的蛋白激酶(AMPK)/核转录因子红系2相关因子2(Nrf2)通路,探讨芍药苷对小鼠溃疡性结
          肠炎(UC)氧化应激的影响及潜在机制。方法  将雄性BALB/c小鼠随机分为对照组,模型组,抑制剂组(AMPK抑制剂Compound
          C 20 mg/kg),芍药苷低、中、高剂量组(芍药苷12.5、25、50 mg/kg)、芍药苷高+抑制剂组(芍药苷50 mg/kg+Compound C 20 mg/kg),
          每组8只。除对照组外,其余各组小鼠均自由饮用4%葡聚糖硫酸钠溶液5 d以构建UC模型。随后,各药物组小鼠灌胃或腹腔注
          射相应药液,每天1次,连续7 d。实验期间,记录各组小鼠体重的变化情况;末次给药24 h后,检测其结肠长度,结肠组织中丙二
          醛(MDA)含量及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性,观察其结肠组织病理学形态、肠上皮细胞间紧密
          连接情况并进行组织病理学评分,检测其结肠组织中 AMPK、Nrf2 mRNA 及 AMPK、Nrf2、血红素加氧酶 1(HO-1)、闭合蛋白
         (occludin)、密封蛋白1(claudin-1)蛋白的表达情况。结果  与模型组比较,芍药苷各剂量组小鼠结肠组织中炎症细胞浸润、隐窝受
          损等病理改变均有所恢复,肠上皮细胞间紧密连接受损情况均有所改善;其体重,结肠长度,SOD、GSH-Px活性,以及AMPK蛋白
          的磷酸化水平,Nrf2、HO-1、occludin、claudin-1蛋白和AMPK、Nrf2 mRNA的表达均显著升高、延长或上调,MDA含量及组织病理
          学评分均显著降低(P<0.05或P<0.01),而抑制剂组上述指标与模型组相当(P>0.05)或更差(P<0.05或P<0.01)。加用抑制剂
          可显著逆转高剂量芍药苷对上述指标的改善作用(P<0.01)。结论  芍药苷可修复小鼠肠上皮细胞损伤,改善上皮细胞间紧密连
          接,并上调相关蛋白、促抗氧化分子的表达和释放,从而改善UC;其作用机制可能与激活AMPK/Nrf2抗氧化通路有关。
          关键词  芍药苷;溃疡性结肠炎;氧化应激;AMPK/Nrf2通路

          Effects and mechanism of paeoniflorin on oxidative stress of ulcerative colitis mice
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          DAI Xin ,WANG Ying ,REN Xinyue ,FAN Dingxing ,LI Xianzhe ,FENG Jiaxuan ,LOU Shilei ,YAN Hui ,
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          SUN Cong(1.  School  of  Pharmacy,  Changchun  University  of  Chinese  Medicine,Changchun  130117,China;
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          2. School of Clinical Medicine,Changchun University of Chinese Medicine,Changchun 130117,China)
          ABSTRACT   OBJECTIVE  To  investigate  the  effects  and  potential  mechanism  of  paeoniflorin  on  oxidative  stress  of  ulcerative
          colitis (UC)  mice  based  on  adenosine  monophosphate-activated  protein  kinase (AMPK)/nuclear  factor-erythroid  2-related  factor  2
         (Nrf2) pathway. METHODS Male BALB/c mice were randomly divided into control group, model group, inhibitor group (AMPK
          inhibitor  Compound  C  20  mg/kg),  paeoniflorin  low-,  medium-  and  high-dose  groups (paeoniflorin  12.5,  25,  50  mg/kg),  high-
          dose  of  paeoniflorin+inhibitor  group (paeoniflorin  50  mg/kg+Compound  C  20  mg/kg),  with  8  mice  in  each  group.  Except  for  the
          control  group,  mice  in  all  other  groups  were  given  4%  dextran  sulfate  sodium  solution  for  5  days  to  establish  the  UC  model.
          Subsequently, mice in each drug group were given the corresponding drug solution intragastrically or intraperitoneally, once a day,
          for 7 consecutive days. The changes in body weight of mice were recorded during the experiment. Twenty-four hours after the last
          administration,  colon  length,  malondialdehyde (MDA)  content,  and  activities  of  superoxide  dismutase (SOD)  and  glutathione
          peroxidase (GSH-Px)  in  colon  tissues  were  measured;  histopathological  morphology  of  colon  tissues,  tight  junctions  between
          intestinal  epithelial  cells,  and  histopathological  scoring  were  all  observed  and  evaluated;  the  mRNA  expressions  of  AMPK  and
          Nrf2, as well as the protein expressions of heme oxygenase-1(HO-1), occludin and claudin-1, were all determined in colon tissue.
          RESULTS  Compared  with  model  group,  paeoniflorin  groups  exhibited  recovery  from  pathological  changes  such  as  inflammatory
                                                             cell  infiltration  and  crypt  damage  in  the  colon  tissue,  as  well
             Δ 基金项目 吉 林 省 自 然 科 学 基 金 项 目(No. YDZJ202401060  as  improved  tight  junction  damage  between  intestinal  epithelial
          ZYTS);吉林省教育厅科学技术研究项目(No.JJKH20230949KJ);长          cells.  Additionally,  significant  increases  or  upregulations  were
          春 中 医 药 大 学 国 家 级 大 学 生 创 新 创 业 训 练 计 划 项 目(No.    observed  in  body  weight,  colon  length,  activities  of  SOD  and
          202210199023)                                      GSH-Px,  phosphorylation  level  of  AMPK,  and  protein
             *第一作者 硕士研究生。研究方向:中药抗炎症性肠病作用机
                                                             expression  of  Nrf2,  HO-1,  occludin,  claudin-1,  and  mRNA
          制。E-mail:1609497176@qq.com
             # 通信作者 教授,硕士生导师,博士。研究方向:中药抗常见多发                 expressions  of  AMPK  and  Nrf2;  concurrently,  MDA  content
          病作用机制。E-mail:37363266@qq.com                       and  histopathological  scores  were  significantly  reduced (P<


          中国药房  2025年第36卷第4期                                                 China Pharmacy  2025 Vol. 36  No. 4    · 427 ·
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