重组水蛭素Ⅲ滴眼液的组织分布和排泄研究  

Study on the Tissue Distribution and Excretion of Recombinant Hirudin Ⅲ

作　　者：江欣[1] 廖建民[1] 杨婷婷[1] 张奉国[1] 吴梧桐[1] 谭树华[1] 

机构地区：[1]中国药科大学生命科学与技术学院,江苏南京210009

出　　处：《药物生物技术》2012年第4期338-342,共5页Pharmaceutical Biotechnology

基　　金：国家"十一五"科技重大专项资助项目(No.2009ZX09103-653)

摘　　要：为了研究重组水蛭素Ⅲ(recombinant hirudin Ⅲ,rHVⅢ)滴眼剂在新西兰兔中的组织分布和粪尿排泄,用氯胺-T法将放射性同位素125I标记到rHVⅢ的酪氨酸残基上,通过同位素示踪方法考察滴眼给药后125I-rHVⅢ在新西兰兔体内的组织分布和粪尿排泄。结果发现新西兰兔滴眼给予125I-rHVⅢ后,125I-rHVⅢ主要通过肾脏排出,给药后120 h通过尿液排出放射性活度占总放射性活度的(81.54±10.78)%,同时通过粪便排出的放射性活度仅为(6.20±2.05)%。将放射性活度高的尿液,经RP-HPLC分离,实验结果表明尿液中存在重组水蛭素Ⅲ原型且比例达23.52%以上。组织分布实验结果表明,rHVⅢ原型及其代谢物在肾脏、血浆分布最多,脑中几乎无分布;rHVⅢ原型及其代谢物在眼部主要分布在角膜及巩膜,房水也有分布,而玻璃体和晶状体几乎没有分布。因此,rHVⅢ主要通过肾脏代谢并以原型和代谢物的形式通过尿液排出体外。In order to study the tissue distribution and the excretion of recombinant hirudin m （ rHVⅢor rHV3 ） eye drops in rab- bits, the isomer ,251 was labeled on the tyrosine of the rHV m by Chloramine-T method. The tissue distribution and the excretion after eye drop 125^I-rHVⅢ were researched by tracing isotopes. The results of urine and feces excretion showed that （81.54 ± 10.78 ） % radioactivity of 125^I-rHVⅢ was excreted from urine when rabbits were given 125^I-rHVⅢ during 120 h, and the feces excretion is （6.20 ± 2.05 ） % at the same period. Using RP-HPLC to separate the urine which contains high activity of radioactivity, the results showed that there was the prototype of rHVm in the urines and the proportion of rHVm was over than 23.52%. The results of tissue distribution experiment showed that the accumulation of 125^I- radiolabeled in the major organs was kidney and plasma and there were barely in brain. In ocular tissues, 125^I-radiolabeled was mostly distributed in cornea and sclera, partly in aqueous humor, and barely in vitreous body and lens. The distribution of 125^I-radiolabeled in left eye was much lower than that of the other one which was in line with the administering right eye. 125^I-rHVⅢ is mainly distributed in kidney and excreted with its metabolites from urine.

关 键 词：重组水蛭素Ⅲ 同位素示踪 氯胺-T法 组织分布 粪尿排泄 RP-HPLC 

分 类 号：Q516[生物学—生物化学]