摘要
目的:将重组人生长激素(rhGH)进行半乳糖化修饰,制得半乳糖化重组人生长激素(Gal-rhGH),并研究其在小鼠体内的分布特征。方法:以D-半乳糖为原料,制得双功能试剂 2-亚氨基-2-甲氧基乙基-1-硫代-β-D-半乳吡喃糖苷(IME),利用IME与重组人生长激素的碱性氨基酸偶合,制得Gal-rhGH。以125I标记Gal-rhGH和rhGH,iv,比较其在小鼠体内的组织分布。结果:差热分析(DTA)证实Gal-rhGH是共价偶联物,平均糖密度为5。Iv后,125I-rhGH-Gal浓集于肝脏,最大分布量是125I-rhGH的2.3倍;在胃脏，最大分布仅为125I-rhGH的43%。Gal-rhGH在血、肝、肾、心、肺、脾、肠中全组织相对放射性分布的ACU分别是rhGH的60%，1.55倍，58%，31%，95%，43%，67%。结论：成功地制备了化学偶联物Gal-rhGH,小鼠体内分布表明其具有明显的肝靶向性。
Abstract
OBJECTIVE:To prepare galactosyl recombinant human growth hormone (Gal-rhGH) and to study its distribution in mice.METHODS:A double-function agent,2-imino-2-methoxyethyl-1-thio-β-D-glycosides(IME) was prepared by D-galactose through acetylation,bromination,condensation,displacement and addition reactions.Gal-rhGH was prepared via IME attaching to the lysine residues on rhGH.RESULTS:Differential thermal analysis (DTA) verified that Gal-rhGH was a covalent compound with mean 5 galactosyl residues per rhGH molecule.The comparative study of distribution in mice after iv showed that the radioactivity of 125I-rhGH-Gal was concentrated in liver,whose maximum quantity was 2.3 times as that of 125I-rhGH.The distribution of 125I-rhGH-Gal in kidney was 43% as that of 125I-rhGH.The AUC of whole tissue relative radioactivity distribution of 125I-rhGH-Gal in blood,liver,kidney,heart,lung,spleen and intestine,were 60%,155%,58%,31%,95%,43%,67% as that of 125I-rhGH,respectively.CONCLUSION:A hepatic targeting agent Gal-rhGH was prepared successfully.
关键词
重组人生长激素 /
半乳糖化人生长激素 /
肝靶向性
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Key words
Recombinant human growth hormone /
Galactosyl recombinant human growth hormone /
hepatic targeting
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李铜铃;李静;庞其捷;贺于玲;宋志平;毛洁;管昌田.
半乳糖化重组人生长激素的制备及其肝靶向性[J]. 中国药学杂志, 1999, 34(09): 600-603
Li Tongling .
Preparation of galactosyl recombinant human growth hormone and its hepatic targeting[J]. Chinese Pharmaceutical Journal, 1999, 34(09): 600-603
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参考文献
1 曾民德．生长激素与肝脏．见：曾民德，萧树东主编．肝脏与内分泌．北京：人民卫生出版，1995：73～79．
2 Jones JI，Clemmon DR．Insulin like growth factors and their binding proteins：biological actions．Endocr Rev，1995，16(1)：3．
3 Ho KY，Kelly JJ．Role of growth hormone in fluid homeostasis．Horm Res，1991，36(Suppl 1)：44．
4 范举正，李铜铃，庞其捷，等．肝靶向抗病毒药 NGA-ACV 的制备及其趋肝性．药学学报，1996，31(8)：585．
5 Franssen EJF，Robert WJ，Mariska V，et al．Hepatic and intrahepatic tareting of an anti-inflammatory agent with human serumalbumin and neoglycoproteins as carrier molecules．Biochem Pharmacol，1993，45(6)：1215．
6 Liang TJ，Makdisi WJ，Sun S，et al．Targeted transfection and expression of hepatitis B viral DNA in human hepatoma cells．J Clin Invet，1993，91(3)：1241．
7 庞其捷，杨麟，钟裕国，等．半乳糖基新糖白蛋白的制备及其对肝特异性受体结合试验的研究.华西医科大学学报，1991，22(4)：368．
8 Ros PH，Hartman HJ，Schlepper-Schafer，et al．Galactose-specific receptors on liver cells：characterization of the purified receptor frommacrophages receptor．Biochim Biophys Acta，1985，847：115．
9 Sxhlepper-Schafer J，Hulsmann D，Djovlcar A，el al．Endocytosisvia galactose receptors in vivo；ligand size directs uptake bvy hepa-tocytesand／or liver macrophages．Exp Cell Res，1986，165：494．
10 Maiter D，Umderwood LE，Maes M，et al．Different effects of intermittent and continuous growth hormone administration on serumsomatomedin-c／imsulin-like growth factor I and liver growth hormone receptors in hypophysectomized rats．En-docrinology，1988，123：1053．
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脚注
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基金
国家自然科学基金资助课题,第39670861号
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