医药导报2011，Vol.30Issue(2)：166-170,5.DOI:10.3870/yydb.2011.02.009
大鼠肝脏和肠道羧酸酯酶CES2对伊立替康的部位特异性代谢作用
Effect of CES2 in Rat Liver and Intestines on the Site-specific Metabolism of Irinotecan
摘要
Abstract
Objective To investigate the expression of carboxylesterases isoenzymes(CES2)in rat liver and intestines, and study its hydrolytic activity to irinotecan (CPT-11 ). Methods CPT-11 was incubated with S9 fractions of rat liver and intestinal tissues and the site-specific hydrolytic activity of CES2 was determined by the formation rate of metabolite SN-38. Furthermore,the mRNA expression of CES2 was detected by real-time fluorescent quantitative reverse transcription-polymerase chain reaction ( RT-PCR). Results The results obtained from the formation of SN-38 showed a site-specific degradation in rat liver and intestine homogenates. Hydrolysis of CPT-11 in homogenates from intestine homogenates was low compared to that from liver homogenates. Segmental difference in intestine was observed in the degradation of CPT-11 as: duodenum＞jejunum＞ileum＞ colon. The mRNA expression levels for the CES2 isozymes AB010635 and AY034877 also indicated that rat liver possessed much higher CES2 activity than intestines, with a gradual decrease of CES2 activity existed along the intestine. Conclusion CPT-11 undergoes conversion to its metabolite in rat liver and intestine S9 fractions, and there is tissue variability in the extent of SN-38 formation, which is associated with the site-specific distribution of CES2 in these tissues. The results provide a basis for the strategies preventing side effects of CPT-11 via CESs inhibition.关键词
伊立替康/肝脏/肠道/羧酸酯酶分类
医药卫生引用本文复制引用
刘东,张程亮,向道春,徐艳娇..大鼠肝脏和肠道羧酸酯酶CES2对伊立替康的部位特异性代谢作用[J].医药导报,2011,30(2):166-170,5.基金项目
中央高校基本科研业务费资助,HUST(项目批号:2010JC057) （项目批号:2010JC057）
