新型维甲酸衍生物ATPR大鼠体内组织分布的研究

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（20 mg·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.