重组人生长激素给药后热损伤大鼠血清和肝脏中胰岛素样生长因子-I表达增加。

Increased expression of insulin-like growth factor-I in serum and liver after recombinant human growth hormone administration in thermally injured rats.

作者信息

Jeschke M G, Chrysopoulo M T, Herndon D N, Wolf S E

机构信息

Department of Surgery, University of Texas Medical Branch, Galveston, Texas, 77550, USA.

出版信息

J Surg Res. 1999 Jul;85(1):171-7. doi: 10.1006/jsre.1999.5623.

DOI:10.1006/jsre.1999.5623

PMID:10383855

Abstract

BACKGROUND

Recombinant human growth hormone (rhGH) has been shown to modulate the hypermetabolic response and the hepatic acute-phase response after thermal injury. In vitro studies, however, demonstrated that rhGH activates insulin-like growth factor-I (IGF-I) gene transcription and production, suggesting that rhGH may exert some of its effects indirectly through IGF-I stimulation. The purpose of this study was to determine the effects of rhGH on serum and hepatic IGF-I in thermally injured rats.

METHODS

Sprague-Dawley rats (56 males) receiving a 60% TBSA third-degree scald burn were randomly divided to receive either rhGH (2.5 mg/kg/day im) or saline (control). Rats were sacrificed on postburn days 1, 2, 5, and 7 and serum IGF-I, hepatic IGF-I mRNA, and IGF-I protein concentration were measured. The physiologic response to changes in IGF-I levels was evaluated by measuring hepatocyte proliferation, total liver protein concentration, and muscle dry/wet weights.

RESULTS

Serum IGF-I was increased from postburn day 1 through day 7 in rats receiving rhGH compared to controls (P < 0.05). Hepatic IGF-I mRNA and IGF-I protein expression were increased from day 1 to 7 after burn in animals receiving rhGH when compared to controls (P < 0.05). Recombinant hGH increased hepatocyte proliferation at 5 days and total liver protein concentration at 5 and 7 days postburn compared to controls (P < 0.05). Muscle dry/wet weights increased in rats receiving rhGH at 7 days after burn compared to controls (P < 0.05).

SUMMARY

Liver and serum IGF-I levels decreased after a thermal injury. Recombinant hGH attenuated this decrease by stimulating hepatic IGF-I expression. Increases in IGF-I were associated with increases in hepatocyte proliferation and protein concentration in liver and muscle.

CONCLUSION

We suggest that rhGH modulates the hypermetabolic response through IGF-I stimulation in the hepatic parenchyma.

摘要

背景

重组人生长激素（rhGH）已被证明可调节热损伤后的高代谢反应和肝脏急性期反应。然而，体外研究表明，rhGH可激活胰岛素样生长因子-I（IGF-I）基因转录和产生，提示rhGH可能通过刺激IGF-I间接发挥某些作用。本研究旨在确定rhGH对热损伤大鼠血清和肝脏IGF-I的影响。

方法

将56只接受60%体表面积三度烫伤的Sprague-Dawley雄性大鼠随机分为两组，分别接受rhGH（2.5mg/kg/天，肌肉注射）或生理盐水（对照组）。在烧伤后第1、2、5和7天处死大鼠，测量血清IGF-I、肝脏IGF-I mRNA和IGF-I蛋白浓度。通过测量肝细胞增殖、肝脏总蛋白浓度和肌肉干/湿重评估对IGF-I水平变化的生理反应。

结果

与对照组相比，接受rhGH的大鼠血清IGF-I从烧伤后第1天至第7天升高（P<0.05）。与对照组相比，接受rhGH的动物烧伤后第1天至第7天肝脏IGF-I mRNA和IGF-I蛋白表达增加（P<0.05）。与对照组相比，重组hGH在烧伤后第5天增加肝细胞增殖，在烧伤后第5天和第7天增加肝脏总蛋白浓度（P<0.05）。与对照组相比，接受rhGH的大鼠在烧伤后第7天肌肉干/湿重增加（P<0.05）。