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落新妇苷对大鼠心肌缺血再灌注损伤的影响及机制
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          陈兴华 ,韩 露 ,贡 鸣 ,张继倬 (1.首都医科大学附属北京世纪坛医院心脏外科,北京 100038;2.首都医
          科大学附属朝阳医院医学研究中心,北京 100020;3.首都医科大学附属北京安贞医院心外科,北京 100029)
          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2023)10-1193-07
          DOI  10.6039/j.issn.1001-0408.2023.10.08

          摘  要  目的  探究落新妇苷(AST)对大鼠心肌缺血再灌注损伤(MIRI)的影响,以及可能的作用机制。方法  将SD雄性大鼠随
          机分为假手术组、模型组、阳性对照组(复方丹参片240 mg/kg)和AST低、高剂量组(30、90 mg/kg)以及AST高剂量+缺氧诱导因子
          1α(HIF-1α)抑制剂组(AST 90 mg/kg+2-甲氧基雌二醇15 mg/kg),每组25只。除假手术组外,其他各组大鼠均建立MIRI模型,灌
          胃或腹腔注射相应药物或生理盐水,连续28 d。测定各组大鼠血清中心肌肌钙蛋白I(cTnI)、肌酸激酶同工酶(CK-MB)含量,测量
          心肌梗死体积比,观察心肌组织病理形态变化、心肌细胞凋亡率和心肌组织线粒体的超微结构,测定心肌组织中肿瘤坏死因子α
         (TNF-α)、白细胞介素 6(IL-6)、丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性以及 HIF-1α、腺病毒 E1B 相互作用蛋白 3
         (BNIP3)、肌球蛋白样 Bcl-2 结合蛋白(Beclin1)的表达,并计算微管相关蛋白轻链 3(LC3)Ⅱ与Ⅰ的比值(简称“LC3Ⅱ/Ⅰ”)。
          结果  与模型组比较,阳性对照组和AST低、高剂量组大鼠的心肌组织无明显肿胀,心肌纤维排列整齐,心肌梗死体积比和cTnI、
          CK-MB、TNF-α、IL-6、MDA含量以及细胞凋亡率均显著降低(P<0.05),SOD活性和HIF-1α、BNIP3、Beclin1蛋白表达量以及LC3
          Ⅱ/Ⅰ均显著升高(P<0.05)。HIF-1α抑制剂可显著削弱AST对MIRI模型大鼠上述指标的改善作用(P<0.05)。结论  AST可以
          通过激活HIF-1α/BNIP3信号通路来增强线粒体自噬,从而减轻大鼠MIRI。
          关键词  落新妇苷;心肌缺血再灌注损伤;缺氧诱导因子1α;B细胞淋巴瘤2/腺病毒E1B相互作用蛋白3;自噬

          Effects and mechanism of astilbin on myocardial ischemia-reperfusion injury in rats
          CHEN Xinghua ,HAN Lu ,GONG Ming ,ZHANG Jizhuo (1.  Dept.  of  Cardiac  Surgery,  Beijing  Shijitan
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          Hospital  Affiliated  to  Capital  Medical  University,Beijing  100038,China;2.  Medical  Research  Center,  Beijing
          Chaoyang Hospital Affiliated to Capital Medical University,Beijing 100020,China;3. Dept. of Cardiac Surgery,
          Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing 100029,China)

          ABSTRACT   OBJECTIVE To investigate the effects of astilbin (AST) on myocardial ischemia-reperfusion injury (MIRI) in rats
          and  its  potential  mechanism.  METHODS  SD  male  rats  were  randomly  divided  into  sham  operation  group,  model  group,  positive
          control group (Compound Salvia miltiorrhiza tablets, 240 mg/kg), AST low-dose and high-dose groups (30, 90 mg/kg), and high-
          dose of AST+hypoxia-inducible factor-1α(HIF-1α) inhibitor group (AST 90 mg/kg+2ME2 15 mg/kg), with 25 rats in each group.
          Except  for  sham  operation  group,  MIRI  model  was  induced  in  other  groups,  and  then  given  relevant  drug  or  normal  saline
          intragastrically  or  intraperitoneally,  for  consecutive  28  d.  Serum  contents  of  cardiac  troponin  I (cTnI)  and  creatine  kinase
          isoenzyme  (CK-MB)  were  detected;  volume  ratio  of  myocardial  infarction  was  measured;  the  pathological  changes  of
          myocardium,  the  apoptotic  rate  of  myocardial  cells  and  ultrastructure  of  mitochondria  in  myocardial  tissue  were  all  observed.  The
          contents  of  tumor  necrosis  factor  α (TNF- α),  interleukin  6 (IL-6)  and  malondialdehyde (MDA),  the  activity  of  superoxide
          dismutase (SOD),  the  expressions  of  HIF-1α,  adenovirus  E1B  interacting  protein  3 (BNIP3)  and  myosin-like  Bcl-2  interacting
          protein (Beclin1) were determined in myocardium. The ratio of microtubule-associated protein light chain 3 (LC3) Ⅱ to Ⅰ (LC3
          Ⅱ/Ⅰ)  in  rat  myocardium  was  calculated.  RESULTS  Compared  with  model  group,  no  obvious  swelling  was  found  in  the
          myocardial  tissue  of  rats  in  positive  control  group, AST  low-dose  and  high-dose  groups,  and  the  myocardial  fibers  were  arranged
          regularly;  the  volume  ratio  of  myocardial  infarction,  the  contents  of  cTnI,  CK-MB,  TNF-α,  IL-6  and  MDA,  the  apoptotic  rate
          were decreased significantly (P<0.05), while SOD activity, protein expressions of HIF-1α, BNIP3 and Beclin1, LC3Ⅱ/Ⅰ were
          increased  significantly (P<0.05).  HIF-1α  inhibitor  could  significantly  weaken  the  improvement  effect  of  AST  on  the  above
          indicators  in  MIRI  model  rats (P<0.05).  CONCLUSIONS  AST  enhances  mitochondrial  autophagy  by  activating  HIF-1α/BNIP3
                                                             signaling pathway, thereby reducing MIRI in rats.
             Δ 基金项目 国家自然科学基金资助项目(No.81770466)                KEYWORDS     astilbin;   myocardial   ischemia-reperfusion
             *第一作者 主治医师,硕士。研究方向:心肌缺血再灌注损伤。                   injury;  hypoxia-inducible  factor-1α;  B-cell  lymphoma-2/
          E-mail:sjtxzwk@163.com                             adenovirus E1B interacting protein 3; autophagy
             # 通信作者 主任医师,硕士。研究方向:心肌缺血再灌注损伤。
          E-mail:13911028861@163.com


          中国药房  2023年第34卷第10期                                              China Pharmacy  2023 Vol. 34  No. 10    · 1193 ·
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