药学学报, 2018, 53(4): 561-566
引用本文:
龚小红, 周忆梦, 郑立, 汤韵秋, 龚莉虹, 余琳媛, 李芸霞, 彭成. 大黄治疗阳虚便秘模型大鼠的整合PK/PD研究[J]. 药学学报, 2018, 53(4): 561-566.
GONG Xiao-hong, ZHOU Yi-meng, ZHENG Li, TANG Yun-qiu, GONG Li-hong, YU Lin-yuan, LI Yun-xia, PENG Cheng. Study on integrated PK/PD of rhubarb in the treatment of yang-deficiency constipation model rats[J]. Acta Pharmaceutica Sinica, 2018, 53(4): 561-566.

大黄治疗阳虚便秘模型大鼠的整合PK/PD研究
龚小红, 周忆梦, 郑立, 汤韵秋, 龚莉虹, 余琳媛, 李芸霞, 彭成
成都中医药大学, 中药资源系统研究与开发利用省部共建国家重点实验室, 培育基地/中药材标准化教育部重点实验室, 四川 成都 611137
摘要:
基于中药系统研究原则建立大黄治疗阳虚便秘大鼠的整合药动学/药效学(pharmacokinetics/phar-macodynamics,PK/PD)模型。采用食醋和冰水活性炭建立大鼠阳虚便秘模型,大黄水煎液按相当于生药2.5 g· kg-1剂量灌胃给药后于0、5、10、15、30、60、120、240、480、720和1440 min时间点眼眶取血0.5 mL,HPLC测定芦荟大黄素、大黄酸、大黄素以及大黄酚的血药浓度,ELISA法测定大鼠血浆中胃动素(motilin,MTL)、胃泌素(gastrin,GT)、内皮素(endothelin,ET)以及血管活性肠肽(vasoactive intestinal peptide,VIP)的活性。采用SPSS 21.0软件进行成分相关性分析以及主成分分析,采用WinNonlin 6.30软件进行整合PK/PD模型拟合。与正常大鼠的药动学参数比较,大黄素在模型大鼠体内表现出吸收好、消除慢的特点;MTL在模型大鼠体内含量明显低于正常大鼠。主成分分析得到浓度和效应的综合值以有滞后时间的Sigmoid-Emax模型连接。建立了大黄治疗阳虚便秘的整合PK/PD模型,为大黄治疗阳虚便秘的物质基础和作用机制提供新的研究方向。
关键词:    大黄      药动学      药效学      主成分分析      整合药动学/药效学     
Study on integrated PK/PD of rhubarb in the treatment of yang-deficiency constipation model rats
GONG Xiao-hong, ZHOU Yi-meng, ZHENG Li, TANG Yun-qiu, GONG Li-hong, YU Lin-yuan, LI Yun-xia, PENG Cheng
State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources Co-founded by Sichuan Province and MOST/The Ministry of Education Key Laboratory of Standardization of Chinese Herbal, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
Abstract:
Study on the integrated pharmacokinetics/pharmacodynamics (PK/PD) model of rhubarb in rats with yang-deficiency constipation based on the principle of traditional Chinese medicine system. The rat model of yang-deficiency constipation was established using vinegar and ice water containing activated carbon. The blood samples with 0.5 mL were collected from orbital venous plexus at 0, 5, 10, 15, 30, 60, 120, 240, 480, 720, 1 440 min time points after oral administration of rhubarb decoction, and the dosage is equivalent to crude drug 2.5 g·kg-1. The concentration of aloe-emodin, rhein, emodin and chrysophanol in rat plasma were determined by HPLC, and ELISA method was used to detect the activities of motilin (MTL), gastrin (GT), endothelin (ET) and vasoactive intestinal peptide (VIP) at different time points in serum. SPSS 21.0 software was used for analysis of component correlation and principal component, and WinNonlin 6.30 software was used to fit PK/PD model. Compared with the pharmacokinetic parameters of normal rats, in addition to emodin in the model rats showed characteristics of good absorption and slow to elimination; the content of MTL in model rats was significantly lower than that in normal rats. The composite values of the concentration and effect obtained by principal component analysis were connected by Sigmoid-Emax model. We established the integrated PK/PD model of rhubarb in treating yang-deficiency constipation to provide a new research direction for the material basis and mechanism of rhubarb treatment of yang deficiency constipation.
Key words:    rhubarb    pharmacokinetics    pharmacodynamics    principal component analysis    integration of pharmacokinetics/pharmacodynamics   
收稿日期: 2017-10-31
DOI: 10.16438/j.0513-4870.2017-1075
基金项目: 国家自然科学基金重点项目(81630101);国家自然科学基金面上项目(81373943);四川省科技厅省青年科技创新研究团队专项计划项目(2017TD0001).
通讯作者: 李芸霞,Tel:86-28-87716140,E-mail:lyxcdutcm@126.com;彭成,E-mail:pengchengsub@126.com
Email: lyxcdutcm@126.com;pengchengsub@126.com
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