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·药学研究·


          清血消脂降糖方对2型糖尿病大鼠胰岛素抵抗的影响及机制                                                                   Δ


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          洪雨欣 ,张 蕾 ,周明学 ,李思耐 ,蔺 莉 ,张 萌 ,郭子轩 ,刘卫红 (1.首都医科大学附属北京中医医院
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          北京市中医药研究所,北京 100010;2.首都医科大学附属北京中医医院疮疡科,北京 100010)
          中图分类号  R285;R965      文献标志码  A      文章编号  1001-0408(2025)01-0024-06
          DOI  10.6039/j.issn.1001-0408.2025.01.05
          摘   要  目的  探讨清血消脂降糖方对2型糖尿病(T2DM)大鼠胰岛素抵抗(IR)的改善作用及潜在机制。方法  采用腹腔注射30
          mg/kg链脲佐菌素联合高脂高糖饲料喂养的方法建立T2DM大鼠模型。实验设置正常对照组,模型组,清血消脂降糖方低、高剂
          量组(6.525、13.05 g/kg,以生药量计)和二甲双胍组(阳性对照,0.18 g/kg),每组8只。给药组大鼠灌胃相应药物,正常对照组、模型
          组大鼠灌胃等体积生理盐水,每日1次,持续6周。测定大鼠体重、空腹血糖(FBG)并进行口服葡萄糖耐量试验,检测大鼠血清中
          空腹胰岛素(FINS)水平并计算胰岛素抵抗指数(HOMA-IR)、胰岛素敏感指数(ISI),检测大鼠血清中血脂四项、肝功能、氧化应激
          指标及炎症因子水平,观察大鼠肝组织病理变化,检测大鼠肝组织中蛋白激酶R样内质网激酶(PERK)、叉头框蛋白O1(FOXO1)
          蛋白磷酸化水平。结果  与模型组相比,清血消脂降糖方高剂量组和二甲双胍组大鼠体重、ISI、高密度脂蛋白胆固醇、超氧化物歧
          化酶水平显著升高(P<0.05),FBG、糖负荷120 min时的血糖值、葡萄糖曲线下面积、FINS、HOMA-IR、低密度脂蛋白胆固醇、总胆
          固醇、甘油三酯、丙氨酸转氨酶、天冬氨酸转氨酶、碱性磷酸酶、丙二醛、白细胞介素6、肿瘤坏死因子α、C反应蛋白水平均显著降
          低(P<0.05),肝组织病理损伤明显改善,肝组织中PERK、FOXO1蛋白磷酸化水平显著降低(P<0.05)。结论  清血消脂降糖方可
          调节糖脂代谢、炎症因子及氧化应激水平,缓解T2DM大鼠IR,其作用机制可能与抑制PERK/FOXO1信号通路有关。
          关键词  清血消脂降糖方;2型糖尿病;胰岛素抵抗;蛋白激酶R样内质网激酶;叉头框蛋白O1

          Effect  and  mechanism  of  Qingxue  xiaozhi  jiangtang  formula  on  insulin  resistance  in  rats  with  type  2
          diabetes mellitus
          HONG Yuxin ,ZHANG Lei ,ZHOU Mingxue ,LI Sinai ,LIN Li ,ZHANG Meng ,GUO Zixuan ,LIU Weihong         1
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         (1. Beijing Institute of Traditional Chinese Medicine, Beijing Hospital of Traditional Chinese Medicine Affiliated
          to Capital Medical University, Beijing 100010, China;2. Dept. of Ulcerative Vascular Surgery, Beijing Hospital
          of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing 100010, China)
          ABSTRACT    OBJECTIVE To investigate the improvement effect and potential mechanism of Qingxue xiaozhi jiangtang formula
          on insulin resistance (IR) in type 2 diabetes mellitus (T2DM) rats. METHODS T2DM rat model was established by intraperitoneal
          injection  of  30  mg/kg  streptozotocin  combined  with  high-fat  and  high-sugar  diet.  The  rats  were  randomly  divided  into  normal
          control group, model group, Qingxue xiaozhi jiangtang formula low-dose and high-dose groups (6.525, 13.05 g/kg, calculated by
          raw  material)  and  metformin  group (positive  control,  0.18  g/kg),  with  8  rats  in  each  group.  Administration  groups  were  given
          relevant  medicine  intragastrically;  normal  control  group  and  model  group  were  given  constant  volume  of  normal  saline
          intragastrically,  once  a  day,  for  consecutive  6  weeks.  Body  mass  and  fasting  blood  glucose (FBG)  were  determined,  and  oral
          glucose  tolerance  test  was  conducted.  Serum  fasting  insulin (FINS)  level  was  measured  to  calculate  the  insulin  resistance  index
         (HOMA-IR)  and  insulin  sensitivity  index (ISI). Additionally,  the  level  of  serum  lipids,  liver  function,  oxidative  stress  indicators
          and  inflammatory  factors  were  assessed.  The  phosphorylation  levels  of  kinase  R-like  endoplasmic  reticulum  kinase (PERK)  and
          forkhead  box  O1 (FOXO1)  protein  in  liver  tissue  of  rats  were  determined.  RESULTS  Compared  with  model  group,  the  body
          weight,  ISI,  the  levels  of  high-density  lipoprotein  cholesterol  and  superoxide  dismutase  were  increased  significantly  in  Qingxue
          xiaozhi  jiangtang  formula  high-dose  group  and  metformin  group (P<0.05);  FBG,  blood  glucose  level  at  120  minutes  of  glucose
          loading,  area  under  the  curve  of  glucose,  FINS,  HOMA-IR,  low-density  lipoprotein  cholesterol,  total  cholesterol,  triglyceride,
          alanine transaminase,  aspartate transaminase,  alkaline phosphatase,  malondialdehyde,  interleukin-6,  tumor necrosis factor-α,  and
                                                              C-reactive  protein  levels  were  significantly  reduced (P<
              Δ 基金项目 国家自然科学基金项目(No.82274284)                  0.05); the pathological damage of liver tissue had significantly
             *第一作者 硕士研究生。研究方向:中医药防治心血管和代谢性
                                                              improved,  and  the  phosphorylation  levels  of  PERK  and
          疾病。E-mail:569798354@qq.com
              # 通信作者 教授,博士生导师,博士。研究方向:中医药防治心血                 FOXO1  proteins  in  liver  tissue  were  significantly  decreased
          管和代谢性疾病。E-mail:liuweihong@bjzhongyi.com            (P<0.05).  CONCLUSIONS  Qingxue  xiaozhi  jiangtang


          · 24 ·    China Pharmacy  2025 Vol. 36  No. 1                                中国药房  2025年第36卷第1期
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