Objective

To investigate the anti-inflammatory property of ghrelin treatment on the Growth Hormone (GH)/Insulin-like Growth Factor-I (IGF-1) axis in Wistar rats that have undergone endotoxemia.

Design

In this randomized animal study, lipopolysaccharide (LPS) (5 mg/kg; intraperitoneal) was administered to induce endotoxemia, and ghrelin (15 nmol/kg; endovenous) was injected simultaneously. Blood and liver samples were collected 2 h, 6 h and 12 h after LPS administration for analysis.

Measurements

Tumor necrosis factor alpha (TNF-α), interleukin (IL)-1, beta (IL-1β), and IL-6 from both blood and liver were determined by ELISA assay. Serum nitrate was determined by chemiluminescense. Growth hormone receptor (GHR) and growth hormone secretagogue receptor 1a (GHSR-1a) were determined by western blotting. GHR mRNA and IGF-1 mRNA were determined by RT-PCR.

Results

LPS administration induced a decrease in IGF-1 and GH serum levels, characterizing GH/IGF-1 axis disruption. Ghrelin treatment attenuated the decrease of serum levels of IGF-1 as well as the increase of TNF-α, IL-1β, IL-6 and nitrate induced by LPS. The increase of induced GHSR-1a protein expression seen in the LPS group after 2 h remained until 6 h after ghrelin treatment. However, attenuation of the circulating IGF-1 decrease by ghrelin treatment was not accompanied by changes in GHR protein expression nor GHR and IGF-1 gene expression.

Conclusion

Ghrelin was able to attenuate changes in the GH/IGF-1 axis observed during systemic inflammation, which may be due to the modulation of pro-inflammatory mediators release.

中文翻译：

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内毒素血症期间生长激素释放肽对生长激素/胰岛素样生长因子-1 轴的作用。

客观的

目的 研究生长素释放肽治疗对患有内毒素血症的 Wistar 大鼠的生长激素 (GH)/胰岛素样生长因子-I (IGF-1) 轴的抗炎特性。

设计

在这项随机动物研究中，给予脂多糖（LPS）（5 mg/kg；腹腔内）以诱导内毒素血症，并同时注射生长素释放肽（15 nmol/kg；静脉内）。LPS给药后2小时、6小时和12小时收集血液和肝脏样本进行分析。

测量

通过 ELISA 测定测定血液和肝脏中的肿瘤坏死因子 α (TNF-α)、白细胞介素 (IL)-1、β (IL-1β) 和 IL-6。通过化学发光法测定血清硝酸盐。通过蛋白质印迹法测定生长激素受体 (GHR) 和生长激素促分泌素受体 1a (GHSR-1a)。通过RT-PCR测定GHR mRNA和IGF-1 mRNA。

结果

LPS 给药诱导 IGF-1 和 GH 血清水平下降，这是 GH/IGF-1 轴破坏的特征。Ghrelin 治疗减弱了 LPS 诱导的血清 IGF-1 水平的降低以及 TNF-α、IL-1β、IL-6 和硝酸盐的增加。LPS 组中 2 小时后观察到的诱导 GHSR-1a 蛋白表达的增加一直持续到 ghrelin 处理后 6 小时。然而，ghrelin 治疗对循环 IGF-1 减少的减弱并不伴随 GHR 蛋白表达或 GHR 和 IGF-1 基因表达的变化。

结论

Ghrelin 能够减弱全身炎症期间观察到的 GH/IGF-1 轴的变化，这可能是由于促炎介质释放的调节所致。