Matejka G L, Bengtsson B A
Department of Internal Medicine, Research Centre for Endocrinology and Metabolism, University of Göteborg, Sahlgrenska Hospital, Sweden.
Growth Horm IGF Res. 1998 Apr;8(2):151-7. doi: 10.1016/s1096-6374(98)80105-6.
The positive effect of insulin-like growth factor I (IGF-I) on the outcome of experimental acute renal failure has gained much attention in recent years. However, the potential positive effects of GH have been less intensively studied. Therefore, a study was designed in which rats suffering from post-ischemic renal failure were treated with high dosage growth hormone (GH). Forty-six rats were subjected to bilateral renal ischemia for 45 min. Following reperfusion the animals were treated with either human recombinant GH in a dosage of 2 mg/day given as subcutaneous injection or placebo. The animals were monitored daily for body weight, s-creatinine, s-urea and B-glucose. S-IGF levels were determined at the start of the experiment and at days 3 and 7. IGF-I and GH receptor mRNA were measured in the kidney and the liver of the surviving animals at the end of the experiment. Survival in the GH-treated rats was 42.9% as compared to 32.0% in the control group (not significant). Both groups of animals lost body weight in the initial phase. The loss in body weight was less pronounced for the GH-treated animals and the difference was significant at day 2 (P<0.05). The s-creatinine levels tended to be lower in the GH-group at all times studied, but the difference was not significant. The s-urea levels were significantly reduced by GH-treatment at day 2 (P<0.05). GH treatment caused no adverse effects on carbohydrate metabolism as studied by daily B-glucose determinations. The serum IGF-I levels were identical in both the groups at day zero. At day 3 the serum IGF-I levels had increased by approximately 30% in both groups. At day 7 the serum IGF-I level was 1600 ng/ml in the GH-treated group as compared to 1400 ng/ml in the placebo group (not significant). When placebo-treated uremic rats were compared to normal sham-operated animals GH-rec mRNA was down-regulated in the kidney and liver, while IGF-I mRNA was down-regulated only in the liver (P<0.05). GH treatment partly restored the GH-rec and IGF-I mRNA levels in both organs. The data are compatible with a severe GH resistance syndrome in acute renal failure.
近年来，胰岛素样生长因子I（IGF-I）对实验性急性肾衰竭结局的积极作用备受关注。然而，生长激素（GH）的潜在积极作用研究较少。因此，设计了一项研究，对缺血后肾衰竭大鼠给予高剂量生长激素（GH）治疗。46只大鼠双侧肾脏缺血45分钟。再灌注后，动物分别接受皮下注射剂量为2mg/天的重组人生长激素或安慰剂治疗。每天监测动物的体重、血清肌酐、血清尿素和血糖。在实验开始时以及第3天和第7天测定血清IGF水平。在实验结束时，测定存活动物肾脏和肝脏中的IGF-I和GH受体mRNA。接受GH治疗的大鼠存活率为42.9%，而对照组为32.0%（无显著差异）。两组动物在初始阶段均体重减轻。接受GH治疗的动物体重减轻不明显，在第2天差异显著（P<0.05）。在所有研究时间点，GH组的血清肌酐水平均有降低趋势，但差异不显著。在第2天，GH治疗使血清尿素水平显著降低（P<0.05）。通过每日测定血糖研究发现，GH治疗对碳水化合物代谢无不良影响。两组在第0天时血清IGF-I水平相同。在第3天，两组血清IGF-I水平均升高约30%。在第7天，接受GH治疗组的血清IGF-I水平为1600ng/ml，而安慰剂组为1400ng/ml（无显著差异）。将接受安慰剂治疗的尿毒症大鼠与正常假手术动物相比，GH受体mRNA在肾脏和肝脏中下调，而IGF-I mRNA仅在肝脏中下调（P<0.05）。GH治疗部分恢复了两个器官中GH受体和IGF-I mRNA水平。这些数据与急性肾衰竭中严重的GH抵抗综合征相符。
