微透析技术结合液质联用的不同剂量黄芪的补阳还五汤在脑缺血损伤大鼠脑药动学研究

doi:10.5246/jcps.2020.02.007

中国药学(英文版) ›› 2020, Vol. 29 ›› Issue (2): 90-101.DOI: 10.5246/jcps.2020.02.007

微透析技术结合液质联用的不同剂量黄芪的补阳还五汤在脑缺血损伤大鼠脑药动学研究

王圣鑫, 闫向丽, 郑昊圳, 余健烨, 余爱明, 沈晓, 王利胜^*

广州中医药大学中药学院, 广东广州 510006

收稿日期:2019-10-12 修回日期:2019-11-23 出版日期:2020-02-29 发布日期:2019-12-15
通讯作者: Tel.: +86-20-39358290, E-mail: wlis68@126.com
基金资助:
National Natural Science Foundation of China (Grant No. 81373973, 81573872, 81873228) and Science and Technology Planning Project of Guangdong Province (Grant No. 2017KZDXM018).

Pharmacokinetics of different dosage of astragalus membranaceus of buyang huanwu decoction in rats with cerebral ischemic injury by microdialysis combined with LC/MS

Shengxin Wang, Xiangli Yan, Haozhen Zheng, Jianye Yu, Aiming Yu, Xiao Shen, Lisheng Wang^*

School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

Received:2019-10-12 Revised:2019-11-23 Online:2020-02-29 Published:2019-12-15
Contact: Tel.: +86-20-39358290, E-mail: wlis68@126.com
Supported by:
National Natural Science Foundation of China (Grant No. 81373973, 81573872, 81873228) and Science and Technology Planning Project of Guangdong Province (Grant No. 2017KZDXM018).

摘要/Abstract

摘要：

探讨不同剂量组的补阳还五汤益气组与活血组有效成分在MCAO大鼠体内的药动学特征。复制大鼠脑缺血再灌注动物模型, 建立补阳还五汤微透析样品的液质联用检测方法, 研究补阳还五汤益气组低、中、高剂(3.09, 6.17, 12.34 g/Kg), 活血组注射液给药剂量为2.32 g/Kg , 股静脉给药后脑缺血再灌注损失大鼠中有效成分的药动学特征。补阳还五汤不同给药组中芒柄花素和芍药苷药动学过程符合一房室模型模型, 低剂量益气组和活血组中芒柄花素和芍药苷的t_1/2分别为(88.43±3.82, 69.18±0.11) min, MRT分别为(138.56±4.83, 113.62±2.42) min, AUC₀_–_t分别为(28 488.35±4800.32, 140 614.80±23 954.05) ng/mL·min; 中剂量益气组和活血组中芒柄花素和芍药苷的t_1/2分别为(82.16±1.78, 67.08±3.69) min, MRT分别为(127.95±2.70, 116.58±4.13) min, AUC₀_–_t (48 619.25±6745.75, 159 026.00±15 003.33) ng/mL·min; 高剂量益气组和活血组中芒柄花素和芍药苷的t_1/2分别为(80.29±1.12, 69.69±0.87) min, MRT分别为(128.79±1.46, 118.78±4.56) min, AUC₀_–_t分别为(109 942.90±13 101.83, 189 417.90±22 311.00) ng/mL·min。高剂量益气组能延长芍药苷t_1/2、MRT, 能延缓芍药苷在脑内被代谢, 有利于芍药苷在脑内维持更持久的作用时间。

关键词: 补阳还五汤, 药动学, 微透析, 脑缺血再灌注

Abstract:

To investigate the pharmacokinetics of effective components of Bu Yang Huang Wu Decoction (BYHWD) with different dosages of Astragalus (Yiqi groups and Huoxue groups ) applicating in rats with middle cerebral artery occlusion (MCAO). Replicating the animal model of cerebral ischemia-reperfusion in rats, establishing the liquid-mass spectrometry method for the determination of BYHWD and researching the pharmacokinetics of effective components of yiqi groups of BYHWD with different dosages of astragalus (3.09, 6.17, 12.34 g/Kg) and Huoxue goups (2.32 g/Kg) when applicated seperately in the rats suffering from cerebral ischemia reperfusion injury after femoral vein administration. The pharmacokinetics of formononetin and paeoniflorin in the different dosage groups of BYHWD met the one-compartment model, and the t_1/2 of formononetin and paeoniflorin in the low-dose Yiqi and Huoxue groups were (88.43±3.82, 69.18±0.11) min, MRT were (138.56±4.83, 113.62±2.42) min, and AUC₀_–_t were (28 488.35±4800.32, 140 614.80±23 954.05) ng/mL·min; The t_1/2 of formononetin and paeoniflorin in the middle-dose Yiqi group and Huoxue group were (82.16±1.78, 67.08±3.69) min, and MRT were (127.95±2.70, 116.58±4.13), AUC₀_–_t were (48 619.25±6745.75, 159 026.00±15 003.33) ng/mL·min; The t_1/2 of formononetin and paeoniflorin in the high-dose Yiqi and Huoxue groups were (80.29±1.12, 69.69±0.87) min, and MRT was (128.79±1.46, 118.78±4.56) min, AUC₀_–_t were (109 942.90±13 101.83, 189 417.90±22 311.00) ng/mL·min. The concentration rate of formononetin t_{1/2 brain}was decreased with increase of Astragalus dose. However, no significant difference between these two variables was found during experiments. Furthermore, the experiments showed that the increasing dose of astragalus would affect the pharmacokinetic behavior of paeoniflorin in the Huoxue groups. More specifically, the result showed that paeoniflorin can be metabolized more slowly in the body when applicated in high dose of the jaundice administration groups . In this way, the effect of paeoniflorin can be lasted for longer time in the body and brain.

Key words: Bu Yang Huan Wu Tang, Pharmacokinetics, Microdialysis, Cerebral ischemia-reperfusion

中图分类号:

R943

Supporting:

王圣鑫, 闫向丽, 郑昊圳, 余健烨, 余爱明, 沈晓, 王利胜. 微透析技术结合液质联用的不同剂量黄芪的补阳还五汤在脑缺血损伤大鼠脑药动学研究[J]. 中国药学(英文版), 2020, 29(2): 90-101.

Shengxin Wang, Xiangli Yan, Haozhen Zheng, Jianye Yu, Aiming Yu, Xiao Shen, Lisheng Wang. Pharmacokinetics of different dosage of astragalus membranaceus of buyang huanwu decoction in rats with cerebral ischemic injury by microdialysis combined with LC/MS[J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(2): 90-101.

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微透析技术结合液质联用的不同剂量黄芪的补阳还五汤在脑缺血损伤大鼠脑药动学研究

Pharmacokinetics of different dosage of astragalus membranaceus of buyang huanwu decoction in rats with cerebral ischemic injury by microdialysis combined with LC/MS

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