新型维甲酸衍生物ATPR大鼠体内组织分布的研究  

Tissue distribution on a novel derivate of all-trans-retinoic acid,ATPR

作　　者：詹侠[1] 陈飞虎[1] 汤继辉[1] 葛金芳[1] 徐亚运[1] 陈冠儒[1] 彭晓清[1] 

机构地区：[1]安徽医科大学药学院,安徽合肥230032

出　　处：《中国药理学通报》2014年第7期985-988,共4页Chinese Pharmacological Bulletin

基　　金：国家科技部"重大新药创制"科技重大专项(No2011ZX09401)

摘　　要：目的建立大鼠组织中新型维甲酸衍生物4-氨基-2-三氟甲基苯基维甲酸酯(ATPR)浓度的测定方法,并研究其在大鼠体内的组织分布。方法 SD大鼠灌胃给药ATPR(20mg·kg-1)和静脉注射给药ATPR(7 mg·kg-1)后,分别于给药后2、4、7 h和5 min、1、5 h取各脏器组织,经预处理,HPLC法测定各组织中ATPR浓度。结果大鼠灌胃ATPR后,肠组织中药物浓度最高,其次在肝、脾、肺组织浓度较高,在心、肾、脂肪和脑组织中浓度较低。静注给ATPR后,肝组织中药物浓度最高,其次在脾、肺组织浓度较高,在心、肾、肠、脂肪和脑组织中浓度较低。结论两种给药途径给药ATPR后,肝组织的药物浓度均较高,提示ATPR在诱导肝癌细胞分化和抗癌细胞增殖方面可能会有较好的靶向作用。Aim To develop a sensitive,specific and accurate method for quantifying a novel derivate of all-trans-retinoic acid, 4-amino-2-trifluoromethyl-phenyl retinate （ATPR）in rat tissues to investigate the tissue distribution of ATPR in rats.Methods Sprague-Daw-ley （SD）rats were killed by exsanguination at 2,4,7 h after a single intragastric administration with one dose of ATPR （20 mg·kg-1 ）or at 5 min,1 h,5 h after a single intravenous administration with one dose of AT-PR （7 mg·kg-1 ）.The concentration of ATPR in the tissues was determined by high performance liquid chromatography （HPLC）method.Results After the rats were administrated intragastrically, the highest concentration of ATPR was observed in intestine,fol-lowed by liver,spleen and lung,while the distribution in heart,kidney,fat and brain was very little.Howev-er,the highest concentration of ATPR was in liver after given intravenously,followed by spleen and lung,and very low in heart,kidney,intestines,fat and brain. Conclusion The distribution of ATPR is higher in liv-er after administrated both intragastrically and intrave-nously,suggesting the potential anti-proliferation and differentiation inducing effects of ATPR targeting at liv-er cancer.

关 键 词：4-氨基-2-三氟甲基苯基维甲酸酯 新型维甲酸衍生物 高效液相色谱法 组织分布 大鼠 静脉注射 灌胃 

分 类 号：R332[医药卫生—人体生理学] R969.1[医药卫生—基础医学]