Page 55 - 《中国药房》2022年4期

参芎葡萄糖注射液在正常和急性心肌缺血大鼠体内的药动学差异 Δ

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张静雅 1，2＊ ，刘利琴 ，李 容 ，陆 苑 ，潘 洁 ，刘 亭 ，孙 佳 （1.贵州医科大学贵州省药物制剂重点实
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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.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 R969.1 文献标志码 A 文章编号 1001-0408（2022）04-0433-06
DOI 10.6039/j.issn.1001-0408.2022.04.09

摘 要 目的 比较参芎葡萄糖注射液（SGI）中盐酸川芎嗪、丹参素、迷迭香酸在正常和急性心肌缺血（AMI）模型大鼠体内的药动
学差异。方法 将雄性 SD 大鼠随机分为正常组和模型组，每组 9 只。模型组大鼠采用盐酸异丙肾上腺素造模法复制 AMI 模型。
每组各取 3 只大鼠进行模型验证后，剩余 6 只大鼠尾静脉注射 SGI（12 mL/kg）或等体积生理盐水，并分别于给药后 0.083、0.167、
0.333、0.5、0.75、1、1.5、2、3、5 h经眼眶静脉丛采血0.3 mL。以木犀草苷为内标，采用超高效液相色谱-串联质谱法检测血浆中盐酸
川芎嗪、丹参素、迷迭香酸的质量浓度，采用WinNonlin 8.1软件拟合药动学参数，采用SPSS 18.0软件进行统计学分析。结果 盐酸
川芎嗪、丹参素、迷迭香酸检测质量浓度的线性范围分别为0.06～29.96、0.01～5.15、0.006～3.09 μg/mL（r均大于0.99），方法学考
察结果均符合 2020 年版《中国药典》的相应要求。与正常大鼠比较，AMI 模型大鼠体内盐酸川芎嗪的 CLz显著升高（P＜0.05）；
丹参素的t1/2和Vz均显著延长或升高（P＜0.05），但cmax和AUC0－5 h均显著降低（P＜0.05）；迷迭香酸的AUC0－5 h显著降低（P＜0.05）。
结论 SGI中的丹参素、迷迭香酸在AMI模型大鼠体内的暴露量均低于正常大鼠，盐酸川芎嗪在AMI模型大鼠体内的消除强于正
常大鼠。
关键词 参芎葡萄糖注射液；急性心肌缺血；超高效液相色谱-串联质谱法；药动学；大鼠

Pharmacokinetic difference of Shenxiong glucose injection in normal and acute myocardial ischemia rats
ZHANG Jingya ，LIU Liqin ，LI Rong ，LU Yuan ，PAN Jie ，LIU Ting ，SUN Jia（1. Guizhou Key Laboratory
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of Pharmaceutics/State Key Laboratory of Efficacy and Utilization of Medicinal Plants，Guizhou Medical
University，Guiyang 550004，China；2. School of Pharmacy，Guizhou Medical University，Guiyang 550004，
China；3. Engineering Research Center for Development and Application of Ethnic Medicine and Traditional
Chinese Medicine of Ministry of Education，Guizhou Medical University， Guiyang 550004，China）
ABSTRACT OBJECTIVE To compare the pharmacokinetics of ligustrazine hydrochloride，salvianic acid and rosemarinic acid
from Shenxiong glucose injection（SGI）in normal and acute myocardial ischemia（AMI）rats. METHODS Male SD rats were
randomly divided into normal group and model group，with 9 rats in each group. AMI model was established by isoproterenol
hydrochloride modeling method. Three rats in each group were selected for model verification. The remaining 6 rats in each group
were given SGI（1.2 mL/kg）or equal volum of normal saline via tail vein；0.3 mL blood was collected through orbital venous
bush 0.083，0.167，0.333，0.5，0.75，1，1.5，2，3，5 h after administration. Using luteoloside as internal standard，the plasma
concentrations of ligustrazine hydrochloride，salvianic acid and rosemarinic acid were determined by ultra performance liquid
chromatography-tandem mass spectrometry. Pharmacokinetic parameters were fitted by WinNonlin 8.1 software，and statistical
analysis was performed by SPSS 18.0 software. RESULTS The linear ranges of ligustrazine hydrochloride，salvianic acid and
rosmarinic acid were 0.06-29.96，0.01-5.15 and 0.006-3.09 μ g/mL （all r＞0.99），respectively. The results of methodological
investigation were all in line with the requirements of Chinese Pharmacopoeia（2020 edition）. Compared with normal rats，CLz of
ligustrazine hydrochloride in AMI model rats was significantly increased（P＜0.05）； t1/2 and Vz of salvianic acid were significantly
prolonged or increased（P＜0.05）；but the cmax and AUC0－5 h were significantly decreased（P＜0.05）；AUC0－5 h of rosmarinic acid
was significantly decreased （P＜0.05）. CONCLUSIONS The exposure levels of salvianic acid and rosmarinic acid in SGI are
lower in AMI model rats than in normal rats，and the elimination of ligustrazine hydrochloride in AMI model rats is stronger than
that in normal rats.
Δ基金项目：国家自然科学基金资助项目（No.81803827）
＊硕士研究生。研究方向：药剂学。电话：0851-86908468。 KEYWORDS Shenxiong glucose injection；acute myocardial
E-mail：19984464787@163.com ischemia； ultra performance liquid chromatography-tandem
# 通信作者：副教授，硕士生导师，博士。研究方向：中药药效物 mass spectrometry；pharmacokinetic；rat
质基础与药动学。电话：0851-86908468。E-mail：392828662@qq.com

中国药房 2022年第33卷第4期 China Pharmacy 2022 Vol. 33 No. 4 ·433 ·