原儿茶醛在脑缺血再灌注损伤模型大鼠血浆及脑组织中的药动学特征研究  

Pharmacokinetic characteristics of protocatechualdehyde in plasma and brain tissue of rats with cerebral ischemia/reperfusion injury

作　　者：杨琼英 宁珑 孙航 冯晋 许春萍 颜明丽 杨茜 何芳雁 YANG Qiong-ying;NING Long;SUN Hang;FENG Jin;XU Chun-ping;YAN Ming-li;YANG Qian;HE Fang-yan(School of Chinese Material Medicine,Yunnan University of Chinese Medicine,Yunnan Kunming 650500,China;Kunming Health Career Academy,Yunnan Kunming 650500,China)

机构地区：[1]云南中医药大学中药学院,云南昆明650500 [2]昆明卫生职业学院,云南昆明650500

出　　处：《中国医院药学杂志》2022年第17期1760-1765,共6页Chinese Journal of Hospital Pharmacy

基　　金：云南省科技厅-科技计划项目(编号:202001AT070138);云南省科技厅-云南中医学院中医联合青年项目[编号:2018FF001(-074)];云南省高层次中医药人才中医药学科后备人才培养项目。

摘　　要：目的:探究原儿茶醛在假手术及脑缺血/再灌注(cerebral ischemia reperfusion injury,CIRI)损伤模型大鼠血浆和脑内的药动学特征。方法:以HPLC法测定原儿茶醛(灌胃:400 mg·kg^(-1))在假手术大鼠和大脑中动脉阻塞/再灌注损伤(middle cerebral artery occlusion/reperfusion,MCAO/R)模型大鼠不同时间点(1,5,10,15,30,45,60,75,90,105,120,150,180,240,360,480 min)的血药浓度,明确其在CIRI病理状态下的血浆药动学特征;同法测定平衡相下(11 min)原儿茶醛在假手术大鼠和MCAO/R模型大鼠脑内不同区域的分布含量,明确其脑组织分布特征;并结合微透析取样技术,测定原儿茶醛(静注:100 mg·kg^(-1))在假手术大鼠和MCAO/R模型大鼠局部脑区不同时间点(0,15,30,45,60 min)的脑药浓度,明确其在大鼠不同脑区的药动学特征。结果:灌胃给予原儿茶醛后,假手术大鼠体内11 min达血药浓度峰值,AUC_(0-t)为(10028.52±2119.42)μg·L^(-1)·h^(-1),t_(1/2)为5.60 h;MCAO/R模型大鼠体内,7.50 min达血药浓度峰值,AUC_(0-t)下降至(6924.17±3627.70)μg·L^(-1)·h^(-1),t_(1/2)为5.31 h;在平衡相下,假手术大鼠的脑内分布浓度为:皮层>纹状体>海马>小脑;MCAO/R模型大鼠的脑内分布浓度为:皮层>小脑>海马>纹状体,病理状态下各脑区分布浓度均明显提高;静注给予原儿茶醛后,假手术大鼠皮层区的AUC_(0-t)为(1295.11±216.57)mg·L^(-1)·min^(-1),T_(max)为30 min,t_(1/2)为17.83 min;MCAO/R模型大鼠皮层区的AUC_(0-t)为(2498.58±128.30)mg·L^(-1)·min^(-1),Tmax为30 min,t_(1/2)为10.35 min。结论:CIRI的病理状态下,大鼠灌胃给予原儿茶醛吸收速度加快,吸收程度下降;脑内暴露量增多,脑内维持时间变短,平衡相下其在皮层区分布浓度最高,CIRI的病理状态会使其脑内分布浓度增加。OBJECTIVE To investigate the pharmacokinetic characteristics of protocatechuic aldehyde in plasma and brain of rats with sham operation and cerebral ischemia reperfusion injury(CIRI).METHODS The blood concentrations of protocatechuic aldehyde(intragastric administration,400 mg·kg^(-1))in sham-operated rats and middle cerebral artery occlusion/reperfusion(MCAO/R)model rats were determined by HPLC at different time points(1,5,10,15,30,45,60,75,90,105,120,150,180,240,360,480 min)to characterize the plasma pharmacokinetics in the pathological state of CIRI.The same method was used to determine the distribution of protocatechualdehyde in different regions of brain of sham-operated rats and MCAO/R rats under equilibrium phase(11 min)to clarify the distribution characteristics of brain tissues.The brain drug concentrations of protocatechuic aldehyde(i.v.,100 mg·kg^(-1))in sham-operated rats and MCAO/R model rats at different time points(0,15,30,45,60 min)were determined by combining with microdialysis sampling technique to clarify the pharmacokinetic characteristics in different brain regions of rats.RESULTS After intragastric administration of protocatechualdehyde,the plasma concentration of normal rats reached the peak value at 11 min,AUC_(0-t) was(10028.52±2119.42)μg·L^(-1)·h^(-1),and t_(1/2) was 5.60 h;as for MCAO/R model rats,the peak plasma concentration was reached at 7.50 min,AUC_(0-t) was decreased to(6924.17±3627.70)μg·L^(-1)·h^(-1),and t_(1/2) was 5.31 h;in the equilibrium phase,the distribution concentration in brain of normal rats was cortex>striatum>hippocampus>cerebellum;that of MCAO/R model rats was cortex>cerebellum>hippocampus>striatum,the distribution concentration in each brain area under pathological conditions was significantly increased;intravenous injection of protocatechualdehyde,the AUC_(0-t) of cortex of normal rats was(1295.11±216.57)mg·L^(-1)·min^(-1),T_(max) was 30 min,and t_(1/2) was 17.83 min;the AUC_(0-t) of cortex of MCAO/R model rats was(2498.58±128.30)mg·L^(-1)·min^(-1

关 键 词：原儿茶醛 药动学 微透析 脑缺血/再灌注损伤 

分 类 号：R969.1[医药卫生—药理学] R285.5[医药卫生—药学]