Bjarnason R, Wickelgren R, Hermansson M, Hammarqvist F, Carlsson B, Carlsson L M
Department of Medicine, International Pediatric Growth Research Center, Goteborg, Sweden.
J Clin Endocrinol Metab. 1998 May;83(5):1566-72. doi: 10.1210/jcem.83.5.4793.
Acquired GH resistance together with reduced skeletal muscle mass are found in patients with increased protein catabolism due, for example, to sepsis, trauma, or major surgery. Both administration of glutamine-containing parenteral nutrition and GH treatment have been found to diminish this catabolism. The effects of GH are mediated in part by insulin-like growth factor I (IGF-I) that is produced in the liver and locally in GH target tissues. The aim of this study was to investigate the effect of GH treatment on expression of the IGF-I gene and GH receptor (GHR) gene in skeletal muscle after major surgery. A new quantitative RT-PCR-based assay was established to measure IGF-I gene expression. Metabolically healthy patients, without significant preoperative weight loss, who were undergoing elective abdominal surgery were included in the study. Five patients (one woman and four men) were treated with daily injections of GH (0.3 IU/kg.day) in addition to being given total parenteral nutrition including glutamine (0.28 g/kg.day). The control group consisted of eight patients (three women and five men), who were given glutamine-enriched total parenteral nutrition but no GH. A muscle biopsy was taken from the lateral portion of the quadriceps femoris muscle preoperatively (day 0) after induction of anesthesia. A second biopsy was taken under local anesthesia on postoperative day 3. Total ribonucleic acid (RNA) was extracted from the muscle biopsies, and IGF-I messenger RNA (mRNA) and GHR mRNA were measured by competitive quantitative RT-PCR assays. IGF-I mRNA and GHR mRNA levels were related to the expression of a housekeeping gene (cyclophilin). In the control group, IGF-I mRNA levels decreased from 1505 +/- 265 (mean +/- SEM) transcripts/cpm cyclophilin on day 0 to 828 +/- 172 on day 3 (P < 0.05). In contrast, IGF-I mRNA levels did not change in the GH-treated group (1188 +/- 400 transcripts/cpm cyclophilin on day 0 vs. 1089 +/- 342 transcripts/cpm cyclophilin on day 3). No statistically significant changes were seen in GHR expression. We conclude that administration of GH prevents the reduction in IGF-I gene expression in skeletal muscle after abdominal surgery.
在因败血症、创伤或大手术等导致蛋白质分解代谢增加的患者中，会出现获得性生长激素抵抗以及骨骼肌质量降低的情况。已发现给予含谷氨酰胺的肠外营养和生长激素治疗均可减少这种分解代谢。生长激素的作用部分是由胰岛素样生长因子I（IGF-I）介导的，IGF-I由肝脏及生长激素靶组织局部产生。本研究的目的是调查大手术后生长激素治疗对骨骼肌中IGF-I基因和生长激素受体（GHR）基因表达的影响。建立了一种基于定量逆转录聚合酶链反应（RT-PCR）的新检测方法来测量IGF-I基因表达。纳入研究的是择期腹部手术且术前体重无显著减轻的代谢健康患者。五名患者（一名女性和四名男性）除接受含谷氨酰胺（0.28 g/kg·天）的全肠外营养外，还每日注射生长激素（0.3 IU/kg·天）。对照组由八名患者（三名女性和五名男性）组成，他们接受富含谷氨酰胺的全肠外营养但未使用生长激素。术前（第0天）麻醉诱导后从股四头肌外侧取肌肉活检样本。术后第3天在局部麻醉下取第二次活检样本。从肌肉活检样本中提取总核糖核酸（RNA），并通过竞争性定量RT-PCR检测法测量IGF-I信使核糖核酸（mRNA）和GHR mRNA。IGF-I mRNA和GHR mRNA水平与管家基因（亲环蛋白）的表达相关。在对照组中，IGF-I mRNA水平从第0天的1505±265（平均值±标准误）转录本/亲环蛋白cpm降至第3天的828±172（P<0.05）。相比之下，生长激素治疗组的IGF-I mRNA水平没有变化（第0天为1188±400转录本/亲环蛋白cpm，第3天为1089±342转录本/亲环蛋白cpm）。GHR表达未见统计学上的显著变化。我们得出结论，生长激素给药可防止腹部手术后骨骼肌中IGF-I基因表达的降低。
