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当归多糖对糖尿病KK-Ay小鼠心肌细胞凋亡的影响
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          崔阳阳 ,杨丽霞 ,米登海 ,魏瑞贤(1.甘肃中医药大学中医临床学院,兰州 730099;2.甘肃省中医药研究院
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          中心实验室,兰州 730050)
          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2023)10-1211-05
          DOI  10.6039/j.issn.1001-0408.2023.10.11

          摘  要  目的  探讨当归多糖对糖尿病KK-Ay小鼠心肌细胞凋亡的影响。方法  将KK-Ay小鼠随机分为模型组、二甲双胍组(200
          mg/kg)和当归多糖高、中、低剂量组(400、200、100 mg/kg),C57BL/6J小鼠作为空白组,每组8只,各组小鼠每日灌胃相应药液或生
          理盐水1次,连续4周。末次给药后,检测小鼠的空腹血糖、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、胰岛素(INS)水平,心
          肌组织中B细胞淋巴瘤2(Bcl-2)、活化的胱天蛋白酶(cleaved-caspase-3)、凋亡信号调节激酶1(ASK1)、磷酸化氨基末端蛋白激酶
         (p-JNK)、磷酸化需肌醇酶1α(p-IRE1α)蛋白表达以及心肌细胞凋亡情况。结果  与模型组比较,二甲双胍组和当归多糖中、高剂
          量组小鼠空腹血糖、TC、LDL-C含量和心肌细胞凋亡率以及p-JNK、p-IRE1α、ASK1、cleaved-caspase-3蛋白表达水平均显著降低,
          INS水平和Bcl-2蛋白表达水平均显著升高(P<0.05或P<0.01)。结论  当归多糖可改善糖尿病KK-Ay小鼠的血糖和血脂水平,
          抑制心肌细胞凋亡,其机制可能与抑制IRE1/ASK1/JNK信号通路有关。
          关键词  当归多糖;糖尿病心肌病;KK-Ay小鼠;细胞凋亡;IRE1/ASK1/JNK信号通路

          Effects of Angelica sinensis polysaccharide on the apoptosis of cardiomyocytes in diabetic KK-Ay mice
          CUI Yangyang ,YANG Lixia ,MI Denghai ,WEI Ruixian(1. Clinical College of Traditional Chinese Medicine,
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          Gansu  University  of  Traditional  Chinese  Medicine,  Lanzhou  730099,  China;2.  Central  Laboratory  of  Gansu
          Provincial Institute of Traditional Chinese Medicine, Lanzhou 730050, China)
          ABSTRACT   OBJECTIVE  To  investigate  the  effects  of Angelica  sinensis  polysaccharide  on  the  apoptosis  of  cardiomyocytes  in

          diabetic  KK-Ay  mice.  METHODS  KK-Ay  mice  were  randomly  divided  into  model  group,  metformin  group (200  mg/kg)  and A.
          sinensis  polysaccharide  high-dose,  medium-dose  and  low-dose  groups (400,  200  and  100  mg/kg);  C57BL/6J  mice  were  included
          in blank group, with 8 mice in each group. Each group was given relevant medicine intragastrically or normal saline, once a day,
          for  consecutive  4  weeks.  After  the  final  administration,  the  levels  of  fasting  glucose,  total  cholesterol (TC),  low-density
          lipoprotein cholesterol (LDL-C) and insulin (INS) were detected; the protein expressions of B-cell lymphoma 2 (Bcl-2), cleaved-
          caspase-3, apoptosis signal-regulated kinase 1 (ASK1), phosphorylated c-Jun N-terminal kinase (p-JNK), phosphorylated inositol-
          requiring  enzyme  1α (p-IRE1α)  in  myocardium,  and  apoptosis  in  cardiomyocytes  were  also  detected.  RESULTS  Compared  with
          model  group,  the  fasting  glucose, TC  and  LDL-C  content,  apoptotic  rate  of  cardiomyocyte,  protein  expressions  of  p-JNK  and  p-
          IRE1α,  ASK1,  cleaved-caspase-3  were  significantly  lower  in  the  metformin  group  and  A.  sinensis  polysaccharide  medium-dose,
          high-dose  groups;  INS  level  and  relative  expression  of  Bcl-2  protein  were  significantly  increased (P<0.05  or  P<0.01).
          CONCLUSIONS  A.  sinensis  polysaccharide  can  improve  the  levels  of  blood  glucose  and  blood  lipid  and  inhibit  cardiomyocyte
          apoptosis in diabetic KK-Ay mice, and the mechanism may be related to the inhibition of IRE1/ASK1/JNK signaling pathway.
          KEYWORDS    Angelica  sinensis  polysaccharide;  diabetic  cardiomyopathy;  KK-Ay  mice;  apoptosis;  IRE1/ASK1/JNK  signaling
          pathway



              随着人们生活水平的逐渐提高,糖尿病的患病率逐                         因 [1―2] 。心血管并发症是糖尿病的主要死亡原因,约44%
          年提升,截至 2030 年,糖尿病全球患病率将上升到                         的1型糖尿病患者和52%的2型糖尿病患者都死于心血
          10.2%(5.78 亿人),将成为造成人们死亡的第七大原                      管 疾 病  [1―2] 。 糖 尿 病 心 肌 病(diabetic  cardiomyopathy,

             Δ 基金项目 甘肃省科技计划项目(No.20JR10RA432)                DCM)是糖尿病导致的主要心血管并发症之一。细胞凋
             *第一作者 硕士研究生。研究方向:中医药防治糖尿病。E-                    亡作为DCM的重要病理特征,参与了DCM病变的整个
          mail:995563704@qq.com
                                                                 [3]
                                                             过程 。内质网应激(endoplasmic reticulum stress,ERS)
             # 通信作者 主任医师,硕士生导师,博士。研究方向:中医药防治
          糖尿病。E-mail:yanglixia-415@163.com                   会 诱 发 需 肌 醇 酶 1α(inositol-requiring  enzyme  1α,

          中国药房  2023年第34卷第10期                                              China Pharmacy  2023 Vol. 34  No. 10    · 1211 ·
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