摘要
研究采用UPLC-MS/MS技术,以正负离子切换,多反应监测模式(MRM)分别同时测定正常生理状态与炎症病理模型大鼠灌胃给药三叶青地上部分抗炎提取物(THAA)后组织中7个抗炎效应组分含量变化,比较不同生理状态下抗炎效应组分群组织分布差异,探讨THAA效应组分群在机体组织器官的分布规律及特性。研究发现,在正常大鼠及炎症病理模型大鼠中,7个效应组分在心、脑、小肠、胃4个脏器组织中均具有较大的药-时曲线下面积(AUC),提示三叶青地上部分抗炎提取物中效应组分群均能透过血脑屏障,且在胃肠道分布较多,推断胃肠道重吸收可能是药物血液分布药-时曲线出现双峰现象的成因之一;与正常大鼠相比,三叶青地上部分抗炎提取物效应组分群在炎症病理模型大鼠的心、脑、小肠、胃、肝、脾、肺、肾、肌肉中,均具有更高的AUC;其中效应组分群在心、脑、小肠、胃中分布较多,提示在病理状态下,机体内脏器组织与三叶青效应组分的结合力可能发生改变且缔合增强,心、脑、小肠、胃可能是THAA在机体内产生抗炎作用的靶效组织;不同生理状态大鼠,THAA效应组分群在各脏器组织中的滞留时间均较短,且相差不大,提示各效应组分在体内均无蓄积作用,炎症病理状态并不影响效应组分群在体内的起效时间。该研究为阐明三叶青地上部分抗炎提取物在机体内靶效组织分布转运规律及特性并进一步指导临床应用提供了实验基础。
The concentrations of seven anti-inflammatory components in blood and tissues were determined by UPLC-MS/MS after oral administration of Tetrastigma hemsleyanum aerial part(THAA)in healthy and inflammatory pathological model rats.The determination was carried out by using positive and negative ion switching technique,and multiple reaction monitoring(MRM)mode.The tissue distributions of the seven components in different physiological states were compared,and the patterns and characteristics of the effective components of THAA were studied.The results revealed that the seven effective components have large drug-time-curve areas(AUC)in heart,brain,small intestine,and stomach in both normal rats and inflammatory pathological model rats.This suggests that the anti-inflammatory effective component groups in THAA extract can all penetrate the blood-brain barrier,and have a large distribution area in gastrointestinal tract.It is inferred that gastrointestinal reabsorption may be one of the causes of the bimodal distribution of the drug-time curve of the drug blood distribution graph.As compared to normal rats,the effective component groups in THAA extract have higher drug-time curve area(AUC)in heart,brain,small intestine,stomach,liver,spleen,lung,kidney,and muscle of inflammatory pathological model rats.Among them,the effective component groups have the largest distribution area in heart,brain,small intestine,and stomach.This suggests that the binding force of organ tissues and drugs in the body may change under pathological conditions.It is speculated that the heart,brain,small intestine,and stomach may be the target tissues of THAA to produce anti-inflammatory effect.The retention times of THAA effective component groups in various organ tissues of rats in different physiological states are all relatively short,and do not have much difference.This suggests that no effective component accumulates in body,and that the pathological state of inflammation does not affect the onset times of the effective component groups.This experiment elucidates the patterns and characteristics of the in vivo target-effecting tissue distribution of THAA anti-inflammatory extract,and provides an experimental basis for clinical treatment.
作者
廖淑彬
陈丹
余文静
熊朝栋
LIAO Shu-bin;CHEN Dan;YU Wen-jing;XIONG Chao-dong(Department of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2021年第5期1224-1249,共26页
China Journal of Chinese Materia Medica
基金
福建省科技引导性项目(2019Y0037)
福建省中医药科技项目(2017FJZYZY202)
福建省科技计划项目(2010Y2004)
中管局中药分析学重点学科校管项目(X2014096-学科)。
关键词
三叶青地上部分抗炎提取物
超高效液相色谱串联质谱
不同生理状态
组织分布
anti-inflammatory extract of Tetrastigma hemsleyanum aerial part(THAA)
UPLC-MS/MS
different physiological states
tissure distribution
