摘要：目的 探讨营养不良、肾病本身和糖皮质激素作为各自独立因素对大鼠血清生长激素结合蛋白(GHBP)及肝脏生长激素受体(CHR)表达的影响，阐明GHBP／GHR改变与肾病综合征(NS)大鼠生长障碍的关系。方法 24只周龄相同体重相近的雄性SD大鼠被随机分成正常、食物对照、阿霉素(5mg·kg)肾病和地塞米松(1．8 mg·kg^-1·d^-1)治疗的阿霉素肾病4组。血清GHBP、GHBP-1浓度及肝脏GHR表达分别采用墨炭包被的葡聚糖蛋白分裂技术、凝胶层析和放射受体分析法检测。结果 1．和正常及食物对照组大鼠相比，肾病和激素治疗组血清GHBP和肝脏GHR的减低其差异有显著性意义，但食物对照组较正常组，激素治疗组较肾病组之减低，其差异无显著意义。2．血清GHBP-1浓度依正常、食物对照、肾病和激素治疗组顺序逐一减低。3．血清GHBP浓度及肝脏GHR表达与大鼠鼻-尾长度和体重均呈正相关(P均＜0．01)。结论 继发性营养不良和肾病本身所致的生长障碍与肝脏CHR表达下降引发的生长激素抵抗有关，糖皮质激素治疗后生长激素抵抗加重也是其生长障碍加剧的重要因素。

Serum growth hormone binding protein and liver growth hormone receptor in nephrotic rats with growth failure

LIU Jianhua ,YI Zhuwen ,ZHAN?Baolin.

(Department of Pediatrics, Second Affiliated Hospital,Hunan Medical University, Changsha 410011, China)

Abstract：Objective To investigate the effects of malnutrition,nephrosis itself and glueocorticoid therapy on serum growth hormone binding protein(GHBP) and liver growth hormone receptor(GHR), and elucidate the relationship between growth failure in nephrotic rats and serum GHBP or liver GHR.Methods Twenty-four male Sprague-Dawley(SD) rats were randomly divided into control,pair-fed,doxorubincin-induced nephrotic(nephrotic) and dexamethasone-treated nephrotic(des-treated) rats.Serum GHBP,GHBP-1 and liver GHR were measured by dextran-coated charcoal technique,gel filtration and radioreceptor assay respectively.Results (1) Serum GHBP and liver GHR were reduced in nephrotic and des-treated rats compared with control and pair-fed rats,but no significant difference was found between control and pair-fed rats or between nephrotic and des-treated rats.(2)Serum GHBP-1 was lower in pair-fed rats,even lower in nephrotic rats and lowest in des-treated rats than in control.(3) There was some significantly positive correlations between nose-tail length or weight and serum GHBP or liver GHR.Conclusions GH resistance,due to decreasd liver GHR,is an important cause of growth failure induced by secondary malnutrition and nephrosis itself.Glucocorticoid therapy deteriorates growth failure by further decreased hepatic GHR.

Keywords：Growth failure;Nephrotic syndrome;Growth hormone receptor;Growth hormone binding protein基金项目：湖南省自然科学基金资助项目[湘科计字97(37-17)]

参考文献：

［1］张星星,易著文,刘建华,等.原发性痛病综合征患儿生长激素/胰岛素样生长因子轴变化与生长障碍.中华儿科杂志,1999,37:235-238.

［2］Maes M,Ketelslegers JM,Underwood LE.Low plasma somatomedin-C in streptozotocin-induced diabetes mellitus.Correlation with changes is somatogenie and lactogenic liver binding sites. Diabetes,1983,32:1060-1069.

［3］Amit T,Barkey R J,Youdim MBH,et al.A new and convenient assay of growth hormone-binding protein activity in human serum.J Clin Endocrinol Metab,1990,71:474-479.

［4］Baumann G,Stolar MW,Amburn K,et al.A specific growth hormone-binding protein in human plasma:initial characterization.J Clin Endocrinol Metab,1986,62:134-142.

［5］Combes S,Louveau L,Bonneau M.Effect of GH administration on GH and IGF-1 receptors in porcine skeletal muscle and liver in relation to plasma GH-binding protein.J Endoerinol,1997,155:19-26.

［6］Dauncey M J,Burton KA,White P,et al.Nutritional regulation of growth hormone receptor gene expression.FASEB J.1994.8:81-88.

［7］Haffner D.Tonshoff B.Blum W.et al.Insulin-like growth factors(IGFs) and IGF binding protein,serum acid-labile subunit and growth hormone binding protein in nephrotic children.Kidney Int,1997,52:802-810.

［8］Thabet MA,Challa A,Chan W,et al.Insulin-like growth factor and growth hormone receptor in nephrotic rats.Am J Physiol.1994,266:E102-E106.

［9］Gabrielsson GB,Carmfignac DF,Flavell DM,et al.Steroid regulation of growth hormone(GH) receptor and GH-binding protein messenger ribonucleic acids in the rat.Endocrinology,1995,136:209-217.

［10］Massa G,Bouillon R,Vanderschueren-Lodeweyckx M.Serum levels of growth hormone-binding protein and insulin-like growth factor-Ⅰ during puberty. Clin Endocrinol,1992,37:175-180.

［11］Carlsson LMS,Attie JM,Compton PG,et al.Reduced concentration of serum growth hormone-binding protein in children with idiopathic short stature.J Clin Endocrinol Metab,1994,78:1325-1330.

［12］Tonshoff B,Cronin MJ,Reichert M,et al.Reduced concentration of serum hormone(GH)-binding protein in children with chronic renal failure:correlation with GH insensitivity.J Clin Endocrinol Metab,1997,82:1007-1013.

［13］Latta K,Krieg RJ,Cjan W,et al.Effects of deflazacort and cortisone on body growth,thymus weight and gene expression of growth-related proteins in the rat.Eur J Endocrinol,1994,131:652-657.

［14］Clark RG,Mortensen DL,Carlsson LMS,et al.Recombinant human growth hormone(GH)-binding protein enhances the growth-promoting activity of human GH in the rat.Endocrinology,1996,137:4308-4315.

收稿日期：1999-10-07