Page 58 - 《中国药房》2023年11期
P. 58

艾纳香总黄酮对急性心肌梗死模型大鼠的药效作用及机制研究
                                                                                                           Δ


                                           1 #
                                                    1
                                                            1
          吕依婷 ,王溢晨 ,冯贻东 ,石忠峰 ,韩 亮 ,张晓琦(1.广东药科大学新药研发中心,广州 510006;2.深圳
                           2
                 1*
                                   2
          海王医药科技研究院有限公司,广东 深圳 518057)
          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2023)11-1332-05
          DOI  10.6039/j.issn.1001-0408.2023.11.09
          摘   要  目的  研究艾纳香总黄酮对急性心肌梗死(AMI)模型大鼠的药效作用及可能机制。方法  采用结扎SD大鼠冠状动脉左
          前降支的方法建立AMI模型。选取造模成功的50只大鼠,按照随机数字表法分为模型组(0.8%羧甲基纤维素溶液)、阳性对照组
         (复方丹参片,300 mg/kg)和艾纳香总黄酮低、中、高剂量组(3、10、30 mg/kg),每组10只;另取10只作为假手术组(0.8%羧甲基纤
          维素溶液)。手术1 d后开始灌胃给药,给药体积均为3 mL/kg,每天给药1次,连续4周。记录术前、术后及每周灌胃给药后大鼠心
          电图S-T段的变化;检测大鼠血流动力学指标[动脉收缩压(SBP)、舒张压(DBP)、平均动脉压(MAP)、左心室收缩压(LVSP)、左心
          室舒张末压(LVEDP)、左心室内压最大上升速率(+LVdp/dtmax )和左心室内压最大下降速率(-LVdp/dtmax )];检测大鼠血清心肌酶
          [乳酸脱氢酶(LDH)、肌酸激酶同工酶-MB(CK-MB)]和炎症因子[肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、IL-1β]水平;检测
          大鼠心肌梗死率和心肌组织中磷脂酰肌醇3激酶(PI3K)、蛋白激酶B(Akt)的磷酸化水平。结果  与模型组比较,给药后各组大鼠
          心电图 S-T 段均显著降低(P<0.05);艾纳香总黄酮中、高剂量组大鼠 SBP、DBP、MAP、LVSP、+LVdp/dtmax、-LVdp/dtmax 及 p-
          PI3K Tyr607 /PI3K、p-Akt Thr308 /Akt、p-Akt ser473 /Akt比值均显著升高(P<0.05),LVEDP、血清心肌酶和炎症因子水平、心肌梗死率均显著降
          低(P<0.05)。结论  艾纳香总黄酮能改善 AMI 模型大鼠的心功能;其作用机制与抑制炎症因子表达,激活 PI3K/Akt 信号通路
          有关。
          关键词  艾纳香总黄酮;急性心肌梗死;磷脂酰肌醇3激酶;蛋白激酶B;心肌保护

          Study  on  the  pharmacodynamics  and  mechanism  of  Blumea  balsamifera  total  flavonoids  against  acute
          myocardial infarction model rats
          LYU Yiting ,WANG Yichen ,FENG Yidong ,SHI Zhongfeng ,HAN Liang ,ZHANG Xiaoqi(1. The Center for
                                   2
                                                 2
                                                                                            1
                    1
                                                                             1
                                                                 1
          Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou 510006, China;2. Shenzhen
          Neptunus Pharmaceutical Research Institute Co., Ltd., Guangdong Shenzhen 518057, China)
          ABSTRACT    OBJECTIVE To  study  pharmacodynamics  and  potential  mechanism  of  Blumea  balsamifera  total  flavonoids  against
          acute myocardial infarction (AMI) model rats. METHODS AMI model of SD rats was established by ligating anterior descending
          branch of left coronary artery. Fifty model rats were randomly divided into model group (0.8% carboxymethyl cellulose solution),
          positive control group (Compound danshen tablet, 300 mg/kg), B. balsamifera total flavonoids low-dose, medium-dose and high-
          dose  groups (3,  10,  30  mg/kg),  with  10  rats  in  each  group.  Other  10  rats  were  included  in  sham  operation  group (0.8%
          carboxymethyl cellulose solution). After 1 day of surgery, they were given relevant medicine 3 mL/kg intragastrically, once a day,
          for  4  consecutive  weeks.  The  changes  of  S-T  segment  were  recorded  before  and  after  operation,  after  weekly  intragastric
          administration. The hemodynamic indexes of rats were all determined, i.e. systolic blood pressure (SBP), diastolic blood pressure
         (DBP),  mean  arterial  pressure (MAP),  left  ventricular  systolic  pressure (LVSP),  left  ventricular  end  diastolic  blood  pressure
         (LVEDP), maximal left ventricular pressure rising rate (+LVdp/dtmax ), maximal left ventricular pressure decreasing rate (-LVdp/
          dtmax ).  The  levels  of  serum  myocardial  enzymes  [lactate  dehydrogenase (LDH),  creatine  kinase  isoenzyme-MB (CK-MB)]  and
          inflammatory  factors  [tumor  necrosis  factor-α (TNF-α),  interleukin-6 (IL-6),  IL-1β]  were  determined. The  myocardial  infarction
          rate of rats and the phosphorylation levels of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) proteins in myocardial
          tissue  were  determined.  RESULTS  Compared  with  model  group,  S-T  segments  of  electrocardiogram  were  all  decreased
          significantly  in  administration  groups (P<0.05).  SBP,  DBP,  MAP,  LVSP,  +LVdp/dtmax,  -LVdp/dtmax,  and  ratio  of  p-PI3K Tyr607 /
                                                              PI3K,  p-Akt Thr308 /Akt,  p-Akt ser473 /Akt  were  increased  significantly
              Δ 基金项目 国家“重大新药创制”科技重大专项(No.2017ZX-              in  B.  balsamifera  total  flavonoids  medium-dose  and  high-dose
          09301036);广东省应用型科技研发专项资金项目(No.2016B02023-           groups (P<0.05).  The  levels  of  LVEDP,  serum  myocardial
          9002)
                                                              enzymes  and  inflammatory  factors,  myocardial  infarction  rate
             *第一作者 硕士研究生。研究方向:药理学。E-mail:yitinglv@
          foxmail.com                                         were  all  decreased  significantly (P<0.05).  CONCLUSIONS
              # 通信作者 副研究员,硕士生导师,博士。研究方向:药理学。E-                B. balsamifera total flavonoids can improve cardiac function of
          mail:propharm@163.com                               AMI  model  rats,  the  mechanism  of  which  may  be  associated


          · 1332 ·    China Pharmacy  2023 Vol. 34  No. 11                            中国药房  2023年第34卷第11期
   53   54   55   56   57   58   59   60   61   62   63