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银杏黄酮苷元减轻多柔比星心脏毒性的作用机制
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          蔡 英    1, 2* ,钱 丽 ,王开靓 ,李 琴 ,刘春花 ,孙 佳 ,潘 洁 ,李勇军 ,陆 苑 (1. 贵州医科大学
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          贵州省药物制剂重点实验室/省部共建药用植物功效与利用国家重点实验室,贵阳 550004;2.贵州医科大学药
          学院,贵阳 550004;3.遵义医科大学基础药理教育部重点实验室,贵州 遵义 563006;4.贵州医科大学民族药
          与中药开发应用教育部工程研究中心,贵阳 550004)
          中图分类号  R965;R285.5      文献标志码  A      文章编号  1001-0408(2024)06-0659-06
          DOI  10.6039/j.issn.1001-0408.2024.06.04

          摘  要  目的  探究银杏黄酮苷元(GA)减轻多柔比星(DOX)心脏毒性的潜在作用机制。方法  将雄性ICR小鼠随机分为对照组
         (CON组)、模型组(DOX组)和GA+DOX组(GDOX组),每组12只。DOX组小鼠隔天尾静脉注射DOX药液3 mg/kg,GDOX组小
          鼠每天灌胃GA混悬液100 mg/kg+隔天尾静脉注射DOX药液3 mg/kg,连续15 d。给药结束后,检测各组小鼠血清中天冬氨酸转
          氨酶(AST)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)水平。基于代谢组学方法,采用超高效液相色谱-四极
          杆静电场轨道阱串联质谱技术,在主成分分析(PCA)、正交偏最小二乘-判别分析(OPLS-DA)的基础上,以变量重要性投影值≥1、
          峰面积差异倍数>1 且 P<0.05 为标准筛选差异代谢物(DEMs),并基于 HMDB、PubChem 等数据库进行生物学分析。结果  与
          CON组比较,DOX组小鼠血清中AST、CK、CK-MB、LDH水平均显著升高(P<0.05);与DOX组比较,GDOX组小鼠血清中上述
          指标(CK-MB除外)水平均显著降低(P<0.05)。PCA、OPLS-DA结果均显示,CON组、DOX组、GDOX组小鼠心脏组织样品均能
          完全分离。经数据库匹配后,鉴定出37个共有DEMs,其中DOX组显著上调而GDOX组显著下调的DEMs有17个,DOX组显著
          下调而GDOX组显著上调的DEMs有8个;涉及通路包括不饱和脂肪酸的生物合成、花生四烯酸代谢、亚油酸代谢、牛磺酸和次牛
          磺酸代谢,关键代谢物包括二十二碳六烯酸、花生四烯酸、磷脂酰胆碱(16∶0/18∶3)和牛磺酸。结论  GA可能通过作用于二十二碳
          六烯酸、花生四烯酸等关键代谢物来调节不饱和脂肪酸的生物合成、花生四烯酸代谢等代谢途径,进而减轻DOX的心脏毒性。
          关键词  银杏黄酮苷元;多柔比星;心脏毒性;代谢组学

          Mechanism of ginkgo flavonoid aglycone against doxorubicin-induced cardiotoxicity
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          CAI Ying ,QIAN Li ,WANG Kailiang ,LI Qin ,LIU Chunhua ,SUN Jia ,PAN Jie ,LI Yongjun ,LU Yuan     1, 3
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          [1.  Guizhou  Provincial  Key  Laboratory  of  Pharmaceutics  &  State  Key  Laboratory  of  Functions  and Applications
          of  Medicinal  Plants,  Guizhou  Medical  University,  Guiyang  550004,  China;  2.  School  of  Pharmacy,  Guizhou
          Medical  University,  Guiyang  550004,  China;  3.  Key  Laboratory  of  Basic  Pharmacology  of  Ministry  of
          Education,  Zunyi  Medical  University,  Guizhou  Zunyi  563006,  China;  4.  Engineering  Research  Center  for  the
          Development  and  Application  of  Ethnic  Medicine  and  TCM (Ministry  of  Education),  Guizhou  Medical
          University, Guiyang 550004, China]
          ABSTRACT   OBJECTIVE  To  investigate  the  potential  mechanism  of  the  effect  of  ginkgo  flavone  aglycone (GA)  against
          doxorubicin (DOX)-induced  cardiotoxicity.  METHODS  The  male  ICR  mice  were  randomized  into  control  group (CON  group),
          model group (DOX group) and GA+DOX group (GDOX group), with 12 mice in each group. The DOX group was injected with
          DOX solution at a dose of 3 mg/kg via tail vein every other day, and the GDOX group was given GA suspension intragastrically at
          a dose of 100 mg/kg every day+DOX solution at a dose of 3 mg/kg via tail vein every other day, for 15 consecutive days. After the
          end of administration, the serum levels of aspartate aminotransferase(AST), creatine kinase(CK), creatine kinase isoenzyme(CK-
          MB)  and  lactate  dehydrogenase(LDH)  in  mice  were  detected  in  each  group.  Based  on  the  metabolomics  method,  UHPLC-Q-
                                                             Exactive Orbitrap HRMS method was used; based on principal
             Δ 基金项目 国家自然科学基金委-贵州喀斯特中心项目(No.
                                                             component analysis (PCA) and orthogonal partial least squares-
          U1812403-5);贵州省科技计划项目(No. 黔科合基础-ZK〔2022〕一般
                                                             discriminant  analysis (OPLS-DA),  the  differentially  expressed
          374,No.黔科合基础〔2020〕1Y381);贵州省基础药理教育部重点实验
                                                             metabolites  (DEMs)  were  screened  using  the  criteria  of
          室开放课题基金资助项目(No.黔教合KY字〔2022〕395号)
             *第一作者 硕士研究生。研究方向:中药药效物质基础。E-                    variable  importance  in  the  projection≥1,  fold  change  of  peak
          mail:3260638059@qq.com                             area>1  and  P<0.05;  biological  analysis  was  conducted  based
             # 通信作者 副教授,硕士生导师,博士。研究方向:中药药效物质                 on  databases  such  as  HMDB  and  PubChem.  RESULTS
          基础。电话:0851-86908648。E-mail:luyuan@gmc.edu.cn       Compared  with  CON  group,  serum  levels  of AST,  CK,  CK-


          中国药房  2024年第35卷第6期                                                 China Pharmacy  2024 Vol. 35  No. 6    · 659 ·
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