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香芍散结口服液 3 种入血成分在乳腺增生症模型大鼠体内的药

          动学研究
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          张 宇    1, 2* ,李家明 ,彭 丹 ,傅若秋 ,明 月 ,刘正碧 ,王晶晶 ,程诗奇 ,谢红军 ,刘 耀 (1. 西藏大学
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          医学院,拉萨 850011;2.陆军特色医学中心药剂科,重庆 400042;3.陆军特色医学中心实验动物中心,重庆
          400042)
          中图分类号  R969.1      文献标志码  A      文章编号  1001-0408(2025)06-0680-06
          DOI  10.6039/j.issn.1001-0408.2025.06.07
          摘   要  目的  探究香芍散结口服液3种入血成分(阿魏酸、芍药苷、迷迭香酸)在乳腺增生(HMG)模型大鼠体内的药动学特征。
          方法  选择雌性SD大鼠,按体重分为对照组和HMG组,每组6只。HMG组以雌激素+孕激素联合诱导构建HMG模型。造模后,
          两组大鼠均灌胃香芍散结口服液1.485 g/kg(以生药量计),每天1次,连续7 d。分别于首次给药前(0 h)以及末次给药后5、15、30
          min和1、2、4、8、12、24 h采血,以氯唑沙宗为内标,采用超高效液相色谱-四极杆飞行时间质谱技术检测大鼠体内阿魏酸、芍药苷、
          迷迭香酸的血药浓度。运用Phoenix WinNonlin 8.1软件,以非房室模型计算其药动学参数[药时曲线下面积(AUC0-24 h、AUC0-∞)、
          平均滞留时间(MRT0-∞)、半衰期(t1/2 )、达峰时间(tmax )、峰浓度(cmax )]。结果  与对照组比较,HMG 组大鼠体内阿魏酸的 AUC0-24 h、
          AUC0-∞、cmax均显著升高(P<0.05);芍药苷的AUC0-24 h、AUC0-∞、MRT0-∞、t1/2、cmax虽有上升或延长趋势,但组间比较差异均无统计学
          意义(P>0.05);迷迭香酸的AUC0-24 h、MRT0-∞均显著升高或延长(P<0.05)。结论  在HMG 模型大鼠体内,香芍散结口服液中的
          阿魏酸、芍药苷、迷迭香酸的体内暴露量均有所增加,迷迭香酸的体内滞留时间明显延长。
          关键词  香芍散结口服液;乳腺增生;阿魏酸;芍药苷;迷迭香酸;药动学;超高效液相色谱-四极杆飞行时间质谱

          Pharmacokinetic  study  of  3  blood-absorbed  components  of  Xiangshao  sanjie  oral  liquid  in  rats  with
          hyperplasia of mammary gland
          ZHANG Yu ,LI Jiaming ,PENG Dan ,FU Ruoqiu ,MING Yue ,LIU Zhengbi ,WANG Jingjing ,CHENG
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          Shiqi ,XIE Hongjun ,LIU Yao (1.  School  of  Medicine,  Tibet  University,  Lhasa  850011,  China;2.  Dept.  of
          Pharmacy,  Army  Medical  Center  of  PLA,  Chongqing  400042,  China;3.  Laboratory  Animal  Center,  Army
          Medical Center of PLA, Chongqing 400042, China)
          ABSTRACT      OBJECTIVE  To  explore  the  pharmacokinetic  characteristics  of  3  blood-absorbed  components  of  Xiangshao  sanjie
          oral  liquid  in  rats  with  hyperplasia  of  mammary  gland (HMG).  METHODS  Female  SD  rats  were  divided  into  control  group  and
          HMG  group  according  to  body  weight,  with  6  rats  in  each  group.  The  HMG  group  was  given  estrogen+progesterone  to  construct
          HMG  model.  After  modeling,  two  groups  were  given  1.485  g/kg  of  Xiangshao  sanjie  oral  liquid (calculated  by  crude  drug)
          intragastrically, once a day, for 7 consecutive days. Blood samples were collected before the first administration (0 h), and at 5,
          15,  30  minutes  and  1,  2,  4,  8,  12,  24  hours  after  the  last  administration,  respectively.  Using  chlorzoxazone  as  the  internal
          standard,  the  plasma  concentrations  of  ferulic  acid,  paeoniflorin  and  rosmarinic  acid  in  rats  were  detected  by  UPLC-Q/TOF-MS.
          The  pharmacokinetic  parameters  [area  under  the  drug  time  curve (AUC0-24 h, AUC0-∞),  mean  residence  time (MRT0-∞),  half-life
         (t1/2 ),  peak  time (tmax ),  peak  concentration (cmax )]  were  calculated  by  the  non-atrioventricular  model  using  Phoenix WinNonlin  8.1
          software.  RESULTS  Compared  with  the  control  group,  the  AUC0-24 h,  AUC0-∞  and  cmax  of  ferulic  acid  in  the  HMG  group  were
          significantly  increased (P<0.05);  the  AUC0-24 h,  AUC0-∞ ,  MRT0-∞ ,  t1/2  and  cmax  of  paeoniflorin  increased,  but  there  was  no
          significant  difference  between  2  groups (P>0.05);  the  AUC0-24 h  and  MRT0-∞  of  rosmarinic  acid  were  significantly  increased  or
          prolonged (P<0.05).  CONCLUSIONS  In  HMG  model  rats,  the  exposure  of  ferulic  acid,  paeoniflorin  and  rosmarinic  acid  in
                                                              Xiangshao  sanjie  oral  liquid  all  increase,  and  the  retention
              Δ  基金项目 重 庆 市 科 卫 联 合 医 学 中 医 药 科 研 项 目(No.
                                                              time of rosmarinic acid is significantly prolonged.
          2023ZDXM032)                                        KEYWORDS    Xiangshao  sanjie  oral  liquid;  hyperplasia  of
             *第一作者 中药师,硕士研究生。研究方向:中药药动学。E-
                                                              mammary  gland;  ferulic  acid;  paeoniflorin;  rosmarinic  acid;
          mail:zhangyu0501@tmmu.edu.cn
                                                              pharmacokinetics; UPLC-Q/TOF-MS
              # 通信作者 副主任药师,博士。研究方向:中药药效物质基础与
          药动学。E-mail:liuyao@tmmu.edu.cn


          · 680 ·    China Pharmacy  2025 Vol. 36  No. 6                               中国药房  2025年第36卷第6期
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