灯盏甲素在大鼠脑缺血再灌注损伤模型的PK-PD结合模型研究

Study on The PK-PD Model of Apigenin-7-O-glucronide Based on The Cerebral Ischemia-Reperfusion Injury Model Rats

本研究旨在建立辛芍组方中灯盏甲素的PK-PD结合模型。首先采用液质联用法测定大鼠脑缺血再灌注损伤模型给药后的不同时间点所得血浆样本中灯盏甲素的药物浓度,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两种药效指标(SOD和LDH),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灯盏甲素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,建立辛芍组方中灯盏甲素的PK-PD结合模型。当以SOD为药效指标时,可得辛芍组方中灯盏甲素的PK-PD模型为E=20.67+(1.22×Ce)/(Ce+5.58);当以LDH为药效指标时,可得辛芍组方中代表成分灯盏甲素的PK-PD模型为E=214.17-(32.72×Ce)/(Ce+0.08)。结果表明,SOD和LDH的浓度与灯盏甲素的浓度存在一定的相关性。辛芍组方及其主要活性成分灯盏甲素可通过提高SOD、降低LDH发挥抗氧化作用来实现保护脑缺血再灌注损伤。

To establish the pharmacokinetic-pharmacodynamic(PK-PD)model of apigenin-7-O-glucronide in Xinshao formula.Firstly,in order to get the concentration-time curve of apigenin-7-O-glucronide 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,two kinds of indexes(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 apigenin-7-O-glucronide 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 apigenin-7-O-glucronide has been established.When SOD was used as the index of efficacy,the PK-PD model of apigenin-7-O-glucronide was obtained as E=20.67+(1.22×Ce)/(Ce+5.58);When LDH was used as the index of efficacy,the PK-PD model of apigenin-7-O-glucronide was obtained as E=214.17-(32.72×Ce)/(Ce+0.08).The PK-PD model of apigenin-7-O-glucronide in the formula showed that the concentration of SOD and LDH was correlated with the concentration of apigenin-7-O-glucronide.The formula and its main active compound apigenin-7-O-glucronide could protect cerebral ischemia reperfusion injury by increasing SOD and decreasing LDH.