【摘要】 研究重组人甲状旁腺素1~34肽(recombinant human parathyroid hormone1~34,rhPTH1~34)在小鼠中的组织分布和在大鼠中的排泄,为国产rhPTH1~34申报临床研究提供实验依据。用Iodogen法将放射性同位素125I标记到rhPTH1~34的酪氨酸残基上,通过同位素示踪和反相高效液相色谱法(RP-HPLC)相结合的方法考察皮下给药后,125I-rhPTH1~34在小鼠中的组织分布和在大鼠中的排泄。大鼠皮下给予125I-rhPTH后,125I-rhPTH主要从尿中排出,48 h内通过尿液排出(80.33±3.92)%的放射性活性,而相同时间内通过胆汁和粪便排出的放射性活性仅为(7.12±1.52)%和(2.55±1.28)%。RP-HPLC分离结果表明在0~2 h,2~4 h和4~8 h收集的尿液中有125I-rhPTH1~34原型存在,其含量分别相当于该时段通过尿排出的放射性活性的33.62%,17.23%和16.05%;在胆汁和粪便中没有检测到125I-rhPTH1~34原型。小鼠皮下注射给予125I-rhPTH1~34后,rhPTH1-34主要分布在肾脏,并在给药后25 min达到峰值,此后随着时间的延长其在肾脏中的相对积累系数不断下降;与肾脏不同,rhPTH1-34分布到其他组织中的速度较慢,在给药后120 min相对积累系数才达到峰值;此时rhPTH1~34在各组织中的相对累积系数的的大小为:肾>胃>脾>肺>肌肉>肠>心>肝>骨>脑。rhPTH1~34主要在肾脏代谢并以原形和代谢物的形式通过尿液排出体外。更多还原

【Abstract】 In order to investigate the tissue distribution and excretion of recombinant human parathyroid hormone_1～34(rhPTH_1～34)in rats and mice after sc injection,the isomer ¹²⁵I was labeled on the tyrosine of the rhPTH_1～34 by Iodogen method.The tissue distribution experiment results showed that when mice were given ¹²⁵I-rhPTH_（1～34）by sc injection,the radioactivity of ¹²⁵I-rhPTH_（1～34）is mainly accumulated in kidney and reached the max relative accumulating degree in 25（）min after injection.However,the distribution of ¹²⁵I-rhPTH_1～34 to other tissue is slower in the order of kidney >stomach > spleen > lung > muscle > heart > liver > bone > brain.Most radioactivity（80.33±3.92）% was excreted from urine when rats were given ¹²⁵I-rhPTH_1～34 by sc injection during 48（）h,and the bile and feces excretion is more less at the same time [（7.12±1.52）% and（2.55±1.28）%,respectively].(¹²⁵I-rhP)TH_1～34 is mainly distributed in kidney and excreted with its metabolites from urine.更多还原