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青连宁心胶囊在缺血性心律失常模型大鼠体内的药效学与药动

学研究 Δ

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李 彦 ，孙洪胜 ，李 玥 ，史宝燕 ，张学顺（1.山东中医药大学药学院，济南 250300；2.山东中医药大学附
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属医院药学部，济南 250011）
中图分类号 R541.7；R972 .2；R969.1 文献标志码 A 文章编号 1001-0408（2022）06-0699-07
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DOI 10.6039/j.issn.1001-0408.2022.06.09
摘 要 目的 研究青连宁心胶囊在缺血性心律失常大鼠体内的药效学与药动学。方法 将30只雄性SD大鼠随机分为空白对照
组、模型对照组、青连宁心胶囊组（4.00 g/kg）、青蒿组（1.43 g/kg）和黄连组（0.42 g/kg），每组6只。各药物组大鼠分别连续灌胃相应
药液，模型对照组和空白对照组大鼠灌胃生理盐水，每天1次，连续7 d。末次给药后，除空白对照组外的其余各组大鼠均尾静脉
注射垂体后叶注射液（1单位/kg）制备缺血性心律失常模型，记录各组大鼠的心电图变化情况。另取36只大鼠随机分为青连宁心
胶囊模型组和青连宁心胶囊对照组（4.00 g/kg）、青蒿模型组和青蒿对照组（1.43 g/kg）、黄连模型组和黄连对照组（0.42 g/kg），各模
型组大鼠尾静脉注射垂体后叶注射液（1单位/kg）造模后，各药物组大鼠再单次灌胃相应药液，各对照组大鼠灌胃等体积生理盐
水。在不同时间点（0、0.25、0.75、1、2、4、6、8、12、24 h）于眼眶取血，利用高效液相色谱法测定血浆中盐酸小檗碱与青蒿素的浓度，
通过WinNonlin 7.0软件计算药动学参数。结果 与模型对照组比较，青连宁心胶囊可显著改善模型大鼠的心率减慢，并显著减少
其PR间期、QT间期延长，且效果普遍优于青蒿组和黄连组（P＜0.05）。与青蒿对照组和黄连对照组比较，青连宁心胶囊对照组大
鼠体内盐酸小檗碱和青蒿素的cmax、AUC0－t、AUC0－∞均显著升高，CL均显著降低，青蒿素的t1/2z显著延长（P＜0.05）；与青连宁心胶
囊对照组比较，青连宁心胶囊模型组大鼠体内盐酸小檗碱和青蒿素的cmax （青蒿素除外）、AUC0－t、AUC0－∞、MRT0－t、MRT0－∞ （青蒿
素除外）均显著升高，CL均显著降低（P＜0.05）。结论 青连宁心胶囊对大鼠缺血性心律失常的改善作用优于青蒿、黄连单药，且能
提高模型大鼠体内盐酸小檗碱和青蒿素的吸收，减慢二者的消除。
关键词 青连宁心胶囊；青蒿；黄连；缺血性心律失常；药效学；药动学

Study on pharmacodynamics and pharmacokinetics of Qinglian ningxin capsule in ischemic arrhythmia
model rats
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LI Yan ，SUN Hongsheng ，LI Yue ，SHI Baoyan ，ZHANG Xueshun （1. School of Pharmacy，Shandong
University of Traditional Chinese Medicine，Jinan 250300，China；2. Dept. of Pharmacy，the Affiliated Hospital
of Shandong University of Traditional Chinese Medicine，Jinan 250011，China）
ABSTRACT OBJECTIVE To study the pharmacodynamics and pharmacokinetics of Qinglian ningxin capsule in rats with
ischemic arrhythmia. METHODS Totally 30 male SD rats were randomly divided into blank control group，model control group，
Qinglian ningxin capsule group（4.00 g/kg），Artemisia annua group（1.43 g/kg），Coptis chinensis group（0.42 g/kg），with 6 rats
in each group. Administration groups were given relevant medicine intragastrically；model control group and blank control group
were given normal saline intragastrically，once a day，for consecutive 7 days. After last medication，except for blank control
group， other groups were given Posterior pituitary injection via tail vein （1 u/kg） to induce ischemic arrhythmia model.
electrocardiogram changes of rats in each group were recorded. Another 36 rats were randomly divided into Qinglian ningxin
capsule model group and Qinglian ningxin capsule control group（4.00 g/kg），A. annua model group and A. annua control group
（1.43 g/kg），C. chinensis model group and C. chinensis control group （0.42 g/kg）. After the rats in each model group were
injected with Posterior pituitary injection（1 u/kg）via tail vein，administration groups were given relevant drugs intragastrically，
and control groups were given constant volume of normal saline intragastrically. Blood was taken from the orbit at different time
points（0，0.25，0.75，1，2，4，6，8，12 and 24 h）. The concentrations of berberine hydrochloride and artemisinin in plasma were
determined by HPLC，and the pharmacokinetic parameters were calculated by WinNonlin 7.0 software. RESULTS Compared with
the model control groups，Qinglian ningxin capsule could significantly improve the heart rate slowing of rats and reduced the
prolongation of PR interval and QT interval significantly，and
Δ 基金项目：山东省自然科学基金面上项目（No.ZR2020MH378）；
the effects were generally better than those of A. annua group
山东省中医药科技发展计划项目（No.2019-0077）
＊硕士研究生。研究方向：中药新剂型、实验方剂学。E-mail： and C. chinensis group （P＜0.05）. Compared with A. annua
820687781@qq.com control group and C. chinensis control group，cmax，AUC0 － t
# 通信作者：主任药师，硕士生导师，硕士。研究方向：中药新剂 and AUC0 － ∞ of berberine hydrochloride and artemisinin were
型、中药临床药学。电话：0531-6866616。E-mail：shs7777@163.com increased significantly in Qinglian ningxin capsule control

中国药房 2022年第33卷第6期 China Pharmacy 2022 Vol. 33 No. 6 ·699 ·