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对羟基苯甲醛代谢物4-HBA在大鼠体内的组织分布研究

Tissue distribution of 4-hydroxybenzaldehyde metabolite in rats
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摘要 目的:研究天麻活性成分对羟基苯甲醛(4-HBd)的代谢物对羟基苯甲酸(4-HBA)在大鼠体内的组织分布特征,明确其脑靶向分布特性。方法:采用线栓法复制大鼠大脑中动脉阻塞/再灌注(MCAO/R)模型,以正常大鼠为对照,分别灌胃给予400 mg/kg 4-HBd。建立高效液相色谱(HPLC)法测定药物干预后大鼠不同组织(心、肝、脾、肺、肾、脑)中4-HBA的含量,选用ZORBAX SB-C_(18)色谱柱(4.6 mm×250 mm, 5μm),以乙腈-0.1%冰醋酸水溶液为流动相进行等度洗脱,流速1.0 ml/min,二极管阵列检测器检测波长278 nm,柱温25℃,进样量20μl。并进行方法学考察。结果:所建立的分析方法专属性强、精密度高、稳定性好。正常及MCAO/R模型大鼠灌胃给予4-HBd后,不同组织中均可检测到其代谢物4-HBA,分布规律基本一致,且4-HBA在脑组织的分布浓度最低。结论:大鼠灌胃给予4-HBd后,其代谢物4-HBA无脑靶向分布特征。 Objective:To study the rat tissue distribution characteristics of 4-hydroxybenzoic acid(4-HBA),the metabolite of 4-hydroxybenzaldehyde(4-HBd)in Gastrodiae Rhizoma,and clarify its brain targeting distribution characteristic.Methods:The middle cerebral artery occlusion/reperfusion(MCAO/R)model was replicated in rats by suture-occluded method,and normal rats were used as control.The rats were treated with 4-HBd at dose of 400 mg/kg by intragastric administration.A high performance liquid chromatography(HPLC)method for the determination of 4-HBA in different tissues(heart,liver,spleen,lung,kidney and brain)of rats after drug intervention was established.The determination was performed on a ZORBAX SB-C18 column(4.6 mm×250 mm,5μm)at flow rate of 1.0 ml/min with 0.1%glacial acetic acid containing water-acetonitrile(isocratic elution).The determination wave length of diode array detector was 278 nm,the column temperature was 25℃,and the injection volume was 20μl.And the methodology was investigated.Results:The established analytical method showed strong specificity,high precision and good stability.After intragastric administration of 4-HBd,4-HBA could be detected in different tissues of normal and MCAO/R model rats.There was similar distribution characteristic in normal and model rats,and the concentration of 4-HBA in brain tissue was the lowest.Conclusion:After intragastric administration of 4-HBd,its metabolite 4-HBA shows no brain targeting distribution.
作者 宁珑 孙航 冯晋 杨琼英 周艳凯 何芳雁 NING Long;SUN Hang;FENG Jin;YANG Qiongying;ZHOU Yankai;HE Fangyan(School of Chinese Material Medicine,Yunnan University of Chinese Medicine,Kunming 650000,Yunnan,China)
出处 《上海中医药大学学报》 CAS 2021年第3期65-70,共6页 Academic Journal of Shanghai University of Traditional Chinese Medicine
基金 国家自然科学基金资助项目(81660677) 云南省科技厅科技计划项目基础研究专项(202001AT070138) 云南省科技厅科技计划项目中医联合重点项目[2017FF117(-004)] 云南省科技厅科技计划项目中医联合青年项目[2018FF001(-074)] 云南省教育厅科学研究基金项目(2020Y0212)。
关键词 对羟基苯甲醛 对羟基苯甲酸 缺血/再灌注损伤 高效液相色谱 大鼠 4-hydroxybenzaldehyde 4-hydroxybenzoic acid ischemia/reperfusion injury high performance liquid chromatography rat
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