营养肾病和糖皮质激素对大鼠肝肾组织IGF-I/IGFBPs mRNA表达的影响

Effects of Nutrition, Nephrosis and Glucocorticoid on IGF-I and IGFBPs mRNA Expressions in the Rat Liver and Kidney

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肝肾组织胰岛素样生长因子I/胰岛素样生长因子结合蛋白(IGF-I/IGFBPs) mRNA表达和血清浓度的影响。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对照、食物对照、阿霉素肾病和地塞米松治疗肾病4组。血清IGF-I/IGFBPs和肝肾组织IGF-I/IGFBPs mRNA表达分别采用RIA，Western ligand blot和RT-PCR法检测。结果：①营养不良大鼠血清IGF-I减低，肝肾组织IGF-I mRNA表达增高；肾病本身对血清IGF-I，肝脏IGF-IA mRNA表达无影响，肾脏表达减低；激素治疗使血清IGF-I，肝肾组织IGF-IA mRNA表达均下降。②营养不良大鼠血清IGFBP-2，肝脏IGFBP-2 mRNA表达减低，肾脏表达正常；肾病本身使大鼠血清IGFBP-2，肝脏IGFBP-2 mRNA表达增高，肾脏表达减低；激素治疗使肝肾组织IGFBP-2 mRNA表达均下降，但对血清浓度无影响。③营养不良大鼠血清IGFBP-3减低，肝脏IGFBP-3 mRNA表达正常；肾病本身使血清IGFBP-3，肝脏IGFBP-3 mRNA表达均下降；激素治疗使血清IGFBP-3增高，但肝脏IGFBP-3 mRNA表达下降。肾脏IGFBP-3 mRNA表达仅在激素治疗组大鼠能检测到。结论：营养、肾病和糖皮质激素对大鼠肝肾组织IGF-I/IGFBPs mRNA表达的调节具有器官特异性；除血清IGF-I减低部分源于肾脏合成下降外，血清IGFBPs紊乱主要与肝脏合成有关；肾病时IGFBPs可能在不同的水平对IGF-I生物效应发挥调节作用。

Abstract:

OBJECTIVE: To investigate the effects of malnutrition, nephrosis itself and glucocorticoid therapy on IGF-I/IGFBPs mRNA expressions in the rat liver and kidney, and serum peptides. METHODS: Twenty four male SpragueDawley (SD) rats were randomly grouped into control, pair fed, doxorubincininduced nephrotic and examethasonetreated nephrotic rats. IGF-I/IGFBPs mRNA in the rat liver and kidney, and serum peptides were measured by RT-PCR, RIA and Western ligand blot respectively. RESULTS: ①Reduced serum IGF-I was caused by malnutrition and glucocorticoid therapy rather than nephrosis itself, but IGF-IA mRNA in rat liver and kidney was increased during malnutrition, reduced during glucocorticoid therapy, and unchanged during nephrosis. ②IGFBP-2 mRNA in the rat liver and serum peptides decreased during malnutrition, and were elevated during nephrosis, but serum IGFBP-2 was not changed during glucocorticoid therapy despite its diminished gene expression in the rat liver and kidney. However, IGFBP-2 mRNA in the rat kidney was unchanged during malnutrition, and reduced during nephrosis. ③Serum IGFBP-3 decreased during malnutrition and nephrosis, and increased during glucocorticoid therapy, but reduced IGFBP-3 mRNA in the rat liver was observed during nephrosis and glucocorticoid therapy rather than malnutrition. IGFBP-3 mRNA in the rat kidney was only detectable during glucocorticoid therapy. CONCLUSIONS: The regulation of nutrition, nephrosis and glucocorticoid on IGF-I/IGFBPsd mRNA expressions in the rat liver and kidney is organspecific. The disturbance of serum IGFBPs in the nephrotic syndrome are mainly due to altered liver synthesis except that low serum IGF-I is partly caused by reduced renal synthesis. IGFBPs might regulate the action of IGF-I at different levels in the nephrotic syndrome.