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黄芩苷对妊娠期糖尿病大鼠胰岛素抵抗的影响及机制
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          石克威 ,陈 曦 ,赵晓燕 ,杨 博 ,刘云春 ,高月月(1.河北北方学院附属第一医院妇产科,河北 张家口
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          075000;2.河北北方学院附属第一医院超声医学科,河北 张家口 075000)
          中图分类号  R965;R285.5      文献标志码  A      文章编号  1001-0408(2026)04-0450-06
          DOI  10.6039/j.issn.1001-0408.2026.04.07
          摘   要  目的  基于腺苷一磷酸活化蛋白激酶(AMPK)/杂色抑制因子3-9同源物1(SUV39H1)/组蛋白H3第9位赖氨酸三甲基化
         (H3K9me3)轴,探讨黄芩苷对妊娠期糖尿病(GDM)大鼠胰岛素抵抗的影响及潜在机制。方法  采用高脂饮食联合链脲佐菌素注
          射的方式构建GDM大鼠模型,并将造模成功的大鼠分为GDM组、黄芩苷低剂量组、黄芩苷高剂量组、黄芩苷高剂量+AMPK抑制
          剂(Compound C)组,每组10只;另取10只以普通饲料喂养的妊娠大鼠,作为对照组。各组大鼠灌胃和(或)腹腔注射相应药液/生
          理盐水,每天1次,连续2周。末次给药后,检测各组大鼠的空腹血糖(FBG)、胰岛功能指标[空腹胰岛素(FINS)、胰岛素抵抗指数
         (HOMA-IR)、胰岛素敏感指数(ISI)]、血脂指标(总胆固醇、甘油三酯、低密度脂蛋白胆固醇)、肝功能指标(丙氨酸转氨酶、天冬氨
          酸转氨酶、碱性磷酸酶)、炎症因子(C反应蛋白、白细胞介素1β、白细胞介素6)、代谢调节蛋白[补体C1q/肿瘤坏死因子相关蛋白3
         (CTRP3)]、胰岛素敏感性相关因子[葡萄糖转运蛋白4(GLUT4)、脂联素]以及氧化应激指标[超氧化物歧化酶(SOD)、过氧化氢酶
         (CAT)、丙二醛(MDA)]水平,观察其肝组织病理改变,并检测肝组织中AMPK/SUV39H1/H3K9me3轴相关蛋白的表达情况。结果
          与GDM组相比,黄芩苷低、高剂量组大鼠肝组织细胞排列紊乱、空泡变性、脂肪沉积、炎症细胞浸润等病理改变均有不同程度改
          善,其FBG、FINS水平,HOMA-IR,血脂指标、肝功能指标、炎症因子、MDA水平以及SUV39H1、H3K9me3蛋白的表达均显著降低
          或下调,代谢调节蛋白、胰岛素敏感性相关因子水平和AMPK蛋白的磷酸化水平均显著升高(P<0.05),且黄芩苷高剂量组的改善
          更显著(P<0.05)。Compound C 可显著逆转高剂量黄芩苷对上述定量指标的改善作用(P<0.05)。结论  黄芩苷可显著减轻
          GDM大鼠的氧化应激和炎症反应,提高体内CTRP3、GLUT4、脂联素水平,从而改善其胰岛素抵抗;上述作用可能与激活AMPK、
          抑制SUV39H1介导的H3K9me3修饰有关。
          关键词  黄芩苷;妊娠期糖尿病;胰岛素抵抗;AMPK/SUV39H1/H3K9me3轴


          Effects of baicalin on insulin resistance in rats with gestational diabetes mellitus and its mechanism
          SHI Kewei ,CHEN Xi ,ZHAO Xiaoyan ,YANG Bo ,LIU Yunchun ,GAO Yueyue(1.  Dept.  of  Obstetrics  and
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          Gynecology,  the  First  Affiliated  Hospital  of  Hebei  North  University,  Hebei  Zhangjiakou  075000,  China;2.
          Dept. of Ultrasound, the First Affiliated Hospital of Hebei North University, Hebei Zhangjiakou 075000, China)
          ABSTRACT    OBJECTIVE  To  investigate  the  effects  of  baicalin (BC)  on  insulin  resistance  in  rats  with  gestational  diabetes
          mellitus (GDM) and its underlying mechanism based on the adenosine monophosphate-activated protein kinase (AMPK)/suppressor
          of variegation 3-9 homolog 1 (SUV39H1)/histone H3 lysine 9 trimethylation (H3K9me3) axis. METHODS A GDM rat model was
          established  by  a  combination  of  a  high-fat  diet  and  streptozotocin  injection.  The  successfully  modeled  rats  were  divided  into  the
          GDM group, BC low-dose group, BC high-dose group, and high-dose of BC+AMPK inhibitor (Compound C) group, with 10 rats
          in each group. Another 10 pregnant rats fed a normal diet served as the control group. Rats in each group were given corresponding
          drugs/normal  saline  intragastrically  and/or  intraperitoneally,  once  daily  for  2  consecutive  weeks. After  the  last  administration,  the
          levels  of  fasting  blood  glucose (FBG),  pancreatic  function  indexes  [fasting  insulin (FINS),  homeostasis  model  assessment  of
          insulin  resistance (HOMA-IR),  insulin  sensitivity  index (ISI)],  blood  lipid  indexes (total  cholesterol,  triglyceride,  low-density
          lipoprotein  cholesterol),  liver  function  indexes (alanine  transferase,  aspartate  transferase,  alkaline  phosphatase),  inflammatory
          indicators (C-reactive protein, interleukin-1β, interleukin-6), metabolic regulatory protein [complement-C1q/tumor necrosis factor-
          related  protein  3 (CTRP3)],  insulin  sensitivity  related  factors  [glucose  transporter  4 (GLUT4),  adiponectin],  and  oxidative  stress
          indicators [superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA)] were measured. Pathological changes in liver
          tissue  were  observed,  and  the  expressions  of  proteins  related  to  the AMPK/SUV39H1/H3K9me3  axis  in  liver  tissue  were  detected.
          RESULTS Compared with the GDM group, rats in the BC low- and high-dose groups showed varying degrees of improvement in
          pathological  changes  such  as  disordered  cell  arrangement,  vacuolar  degeneration,  lipid  deposition,  and  inflammatory  cell
                                                              infiltration in liver tissue. Their FBG and FINS levels, HOMA-
              Δ 基金项目 河北省卫生健康委员会医学科学研究课题计划(No.
                                                              IR,  the  levels  of  blood  lipid  indexes,  liver  function  indexes,
          20231409)
             *第一作者 主治医师,硕士。研究方向:病理产科及母胎医学。                    inflammatory  indicators  and  MDA,  and  the  expressions  of
          E-mail:lxw2l@163.com                                SUV39H1 and H3K9me3 were significantly decreased or down-


          · 450 ·    China Pharmacy  2026 Vol. 37  No. 4                               中国药房  2026年第37卷第4期
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