基于大鼠脑缺血再灌注损伤模型建立芍药内酯苷的PK-PD模型  

Pharmacokinetic-Pharmacodynamic Link Model of Albiflorin Based on Cerebral Ischemia-Reperfusion Injury Model Rats

作　　者：巩仔鹏[1,2,3,4] 李梅 胡建春[1,2,3,4] 吴林霖 王爱民[1,2,3,4] 李勇军 李月婷 

机构地区：[1]贵州医科大学贵州省药物制剂重点实验室,贵州贵阳550004 [2]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,贵州贵阳550004 [3]贵州医科大学药学院,贵州贵阳550004 [4]国家苗药工程研究中心,贵州贵阳550004

出　　处：《安徽农业科学》2017年第27期1-3,共3页Journal of Anhui Agricultural Sciences

基　　金：国家自然科学基金项目(81260636);贵州省优秀青年科技人才培养项目(黔科合人字[2015]11号);贵州省民族药药效物质基础研究科技创新人才团队\贵州省高层次创新型人才培养(百层次黔科合平台人才[2016]5613\5677);贵州省中医药管理局项目(QZZY-2015-080)

摘　　要：[目的]建立芍药内酯苷的药动学-药效学(PK-PD)模型。[方法]首先采用液质联用法测定大鼠脑缺血再灌注损伤模型给予辛芍组方后的不同时间点所得血浆样本中芍药内酯苷的药物浓度,获得药时曲线;同时采用试剂盒测定不同时间点所得血浆样本中的超氧化物歧化酶(SOD)和乳酸脱氢酶(LDH)含量,获得时效曲线。然后用Win Non Lin软件采用房室模型的分析方法对芍药内酯苷的药代动力学参数进行拟合,获得PK参数。在此基础之上,固定相关的药代动力学参数,对时效关系进行拟合,得到相关的PD参数,根据PD参数,建立辛芍组方中芍药内酯苷的PK-PD模型。[结果]当以SOD为药效指标时,可得辛芍组方中芍药内酯苷的PK-PD模型为E=21.04+(7.16×Ce)/(Ce+372.4);当以LDH为药效指标时,可得辛芍组方中代表成分芍药内酯苷的PK-PD模型为E=216.83-(37.31×Ce)/(Ce+0.04)。[结论]SOD和LDH的浓度与芍药内酯苷的浓度存在一定的相关性。芍药内酯苷可通过提高SOD、降低LDH发挥抗氧化作用来实现保护脑缺血再灌注损伤。[Objective] The aim was to establish the pharmacokinetic-pharmacodynamic( PK-PD) model of albiflorin in Xinshao formula.[Method]Firstly,in order to get the drug-time curve of albiflorin in Xinshao formula in plasma collected from different time points of a disease model animal,whose concentration were determined by the method of UPLC-MS. At the same time,the content of SOD and LDH in the plasma samples of different time points were determined by the kit for time-effect curve. Then the pharmacokinetic software was used to fit the pharmacokinetic parameters of albiflorin with the compartmental model and to get PK parameters. After that,the pharmacokinetic parameters were fixed,and the time effect relationship were fitted to get the relevant PD parameters. According to the PD parameters,the PK-PD model of albiflorin had been established. [Result]When SOD was used as the index of efficacy,the PK-PD model of albiflorin was obtained as E = 21. 04 +( 7.16 × Ce)/( Ce +372.4); When LDH was used as the index of efficacy,the PK-PD model of albiflorin was obtained as E = 216. 83-( 37. 31 ×Ce)/( Ce + 0. 04). [Conclusion]The PK-PD model of albiflorin in the formula showed that the concentration of SOD and LDH was correlated with the concentration of albiflorin. Albiflorin could protect cerebral ischemia reperfusion injury by increasing SOD and decreasing LDH.

关 键 词：大鼠脑缺血再灌注损伤模型 辛芍组方 芍药内酯苷 PK-PD模型 

分 类 号：R927.2[医药卫生—药学]