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余甘子水提物对糖尿病模型大鼠脂质代谢紊乱和胰岛素抵抗的

          改善作用及机制研究
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          钟绍金    1, 2* ,韩珊颖 ,何小爱 ,黄裕昌(1. 上海市第六人民医院-海口市骨科与糖尿病医院药学部,海口
          570000;2.中南大学湘雅医学院附属海口医院药学部,海口 570208;3.海南省药物研究所,海口 570311)
          中图分类号  R965.1      文献标志码  A      文章编号  1001-0408(2023)03-0327-06
          DOI  10.6039/j.issn.1001-0408.2023.03.14

          摘  要  目的  探讨余甘子水提物改善糖尿病模型大鼠脂质紊乱和胰岛素抵抗(IR)的作用及可能机制。方法  雄性SD大鼠进行
          IR造模,并随机分为模型组、阳性对照组和余甘子水提物高、中、低剂量组,另设空白组,每组各10只。余甘子水提物高、中、低剂
          量组大鼠分别给予800、400、200 mg/kg余甘子水提物稀释液,阳性对照组大鼠给予2.7 mg/kg吡格列酮溶液,空白组和模型组大鼠
          给予等体积生理盐水,每日灌胃1次,连续4周。观察大鼠一般状态并测定其体质量及血清脂代谢指标[三酰甘油(TG)、总胆固醇
         (TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)]水平;应用酶联免疫吸附法测定并计算其血清空腹胰岛素
         (FINS)、胰岛素抵抗指数(IRI)及胰岛素敏感指数(ISI);通过苏木素-伊红染色观察其肝组织病理形态;通过碘酸-雪夫(PAS)染色
          法观察其肝组织糖原表达情况,并计算染色面积;采用Western blot法检测其肝组织中氧化物酶增殖体激活受体γ(PPARγ)、核因
          子κB(NF-κB)、磷酸化腺苷酸活化蛋白激酶(p-AMPK)蛋白表达。结果  与空白组比较,模型组大鼠多饮、多食、多尿现象明显,其
          血清中TC、TG、LDL-C、FINS水平和IRI显著升高(P<0.05),ISI显著降低(P<0.05);肝小叶结构明显紊乱,肝细胞多发变形、肿
          大,且有许多脂质沉积和脂肪空泡;糖原 PAS 染色面积显著减小(P<0.05);PPARγ、p-AMPK 蛋白表达水平显著降低(P<0.05),
          NF-κB蛋白表达水平显著升高(P<0.05)。与模型组比较,余甘子水提物高、中剂量组大鼠精神状态、肝组织病理形态及糖原表达
          情况均明显好转,以上指标水平均显著逆转(P<0.05)。结论  余甘子水提物可能通过激活PPARγ/AMPK/NF-κB信号通路,改善
          IR模型大鼠的糖脂代谢紊乱、肝功能和IR。
          关键词  余甘子水提物;糖尿病;脂质代谢;胰岛素抵抗;氧化物酶增殖体激活受体γ;核因子κB;磷酸化腺苷酸活化蛋白激酶

          Study  on  the  improvement  effects  and  mechanism  of  Phyllanthus  emblica  water  extracts  on  insulin
          resistance and lipid metabolism disorder in diabetic model rats
          ZHONG Shaojin ,HAN Shanying ,HE Xiaoai ,HUANG Yuchang(1.  Dept.  of  Pharmacy,  Shanghai  Sixth
                        1, 2
                                         2
                                                                       3
                                                     2
          People’s Hospital-Haikou Orthopaedic and Diabetes Hospital, Haikou 570000, China;2. Dept. of Pharmacy, the
          Affiliated  Haikou  Hospital  of  Xiangya  School  of  Medicine,  Central  South  University,  Haikou  570208,  China;
          3. Hainan Institute of Pharmacy, Haikou 570311, China)
          ABSTRACT   OBJECTIVE To investigate the improvement effects and possible mechanism of Phyllanthus emblica water extracts
          on  lipid  metabolism  disorder  and  insulin  resistance (IR)  in  diabetic  model  rats.  METHODS  IR  model  of  male  SD  rats  was
          established and randomly divided into model group, positive control group, P. emblica water extracts high-dose, medium-dose and
          low-dose  groups,  and  another  blank  group  was  set  up,  with  10  rats  in  each  group.  P.  emblica  water  extracts  high-dose,  medium-
          dose  and  low-dose  groups  were  given  P.  emblica  water  extract  diluent  at  the  doses  of  800,  400  and  200  mg/kg  respectively;
          positive  control  group  was  given  pioglitazone  solution  2.7  mg/kg;  blank  group  and  model  group  were  given  the  same  volume  of
          normal  saline,  by  intragastrical  administration,  once  a  day,  for  consecutive  4  weeks. The  general  state  of  rats  was  observed,  and
          the  body  mass  and  the  levels  of  serum  lipid  metabolism  indexes  [triacylglycerol (TG),  total  cholesterol (TC),  low-density
          lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)] were measured; fasting insulin of serum (FINS),
          insulin  resistance  index (IRI)  and  insulin  sensitivity  index (ISI)  were  measured  and  calculated  by  enzyme-linked  immunosorbent
          assay (ELISA).  The  pathological  morphology  of  liver  tissue  was  observed  by  hematoxylin-eosin  staining;  the  expression  of
          glycogen in the liver was observed by periodic acid-Schiff staining, and the staining area was calculated; the protein expressions of
                                                             peroxisome  proliferator-activated  receptor  γ (PPARγ),  nuclear
             Δ 基金项目 海南省重点研发计划项目(No.ZDYF2020171)
                                                             factor κB(NF-κB) and AMP-activated protein kinase (AMPK)
             *第一作者 副主任中药师,硕士。研究方向:药理学。E-mail:
          439238735@qq.com                                   were  detected  by  Western  blot.  RESULTS  Compared  with
             #  通信作者 副 主 任 药 师 。 研 究 方 向 :药 理 学 。 电 话 :0898-  blank  group,  the  rats  in  the  model  group  had  obvious
          68603845。E-mail:1339566230@qq.com                  symptoms  of  polydipsia,  polyphagia  and  polyuria,  and  the


          中国药房  2023年第34卷第3期                                                 China Pharmacy  2023 Vol. 34  No. 3    · 327 ·
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