乙烷硒啉在大鼠和结肠癌荷瘤裸鼠体内的组织分布研究  

Study on tissue distribution of 1,2-[bis(1,2-benzisoselenazolone-3(2H)-ketone)]-ethane in nude mice and SD rats

作　　者：周海燕[1,2] 孟志云[3] 窦桂芳[3] 何铁强[1] 楼雅卿[2] 章国良[2] 

机构地区：[1]中国医学科学院肿瘤医院药剂科,北京100021 [2]北京大学医学部基础医学院药理系,北京100083 [3]军事医学科学院野战输血研究所,北京100850

出　　处：《中国新药杂志》2012年第21期2539-2543,共5页Chinese Journal of New Drugs

基　　金：国家自然科学基金(30973585;91029747);国家“重大新药创制”科技重大专项(2009ZX09301-010)

摘　　要：目的:考察抗肿瘤新药乙烷硒啉在大鼠和结肠癌荷瘤裸鼠体内的组织分布规律。方法:采用荧光分光光度法和液相色谱-质谱联用法分别测定SD大鼠和人结肠癌LS174T细胞荷瘤裸鼠灌服乙烷硒啉后各组织中药物浓度经时变化。结果:大鼠灌服乙烷硒啉2 h后,药物广泛分布于各组织,以胃肠及其内容物、肝、肾中含量最高;24 h肝肾组织硒浓度分别为(6.14±0.87)和(6.93±0.94)μg.g-1,同时间点血液中硒浓度为(4.43±1.65)μg.mL-1;48 h后除肾脏外,其他各组织硒浓度数值均低于血硒浓度。结肠癌裸鼠给药后1 h即可见原形药迅速分布于各组织,至24 h肾脏药物浓度达峰值,而其他组织中药物浓度显著降低,至48 h肿瘤中仍可检测出较高药物浓度。结论:乙烷硒啉口服给药后在大鼠和结肠癌荷瘤裸鼠体内均可广泛分布,并对肿瘤组织具有一定选择性,其组织分布特点可能与药物的代谢排泄途径相关。Objective： To investigate the characteristics of tissue distribution of 1,2-[bis（1,2-benzisoselenazolone-3（2H）-ketone）]-ethane（BBSKE） in nude mice and SD rats.Methods： An atomic fluorescence spectrometry（AFS） was applied to determine the concentrations of selenium in SD rats after administration of BBSKE,and HPLC-MS/MS was applied to determine the concentrations of BBSKE in nude mice after administration of BBSKE.Results： Selenium was observed to widely distribute in various tissues at 2 h after administration of BBSKE in rats.It was shown that selenium mainly existed in the digestive tract including stomach,small intestine,large intestine and their contents,kidney and liver.After 24 h,the concentrations of selenium in liver and kidney were（6.14±0.87） and（6.93±0.94） μg·g-1,respectively,while the average concentration of selenium in plasma was（4.43±1.65） μg·mL^-1.After 48 h,selenium concentration reduced in other tissues except kidney.Similarly,BBSKE was widely distributed in various tissues at 1 h after administration in nude mice grafted with human colon carcinoma LS174T cells.At 24 h,the concentration of BBSKE in kidney reached peak value,however,the concentrations of BBSKE in liver,stomach,small intestine and their contents began to significantly reduce.At 48 h,a higher concentration in tumor was observed,which indicated that BBSKE could reach the tumor location.Conclusion： BBSKE widely distributes in various tissues in nude mice and rats,and shows selectivity for tumors.The characteristic of tissue distribution may be relevant with the metabolism and excretion of BBSKE.

关 键 词：乙烷硒啉 组织分布 荷瘤裸鼠 大鼠 

分 类 号：R979.1[医药卫生—药品] R969.1[医药卫生—药学]