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激素轴、生长激素-IGF-1 在促胃液素治疗胆囊收缩素诱导的急性胰腺炎过程中的作用。

Role of hormonal axis, growth hormone - IGF-1, in the therapeutic effect of ghrelin in the course of cerulein-induced acute pancreatitis.

机构信息

Department of Physiology, Jagiellonian University Medical College, Cracow, Poland.

出版信息

J Physiol Pharmacol. 2010 Oct;61(5):599-606.

PMID:21081804
Abstract

Ghrelin is a ligand for growth hormone secretagogue receptor and stimulates release of growth hormone (GH). Recent studies have shown that treatment with ghrelin exhibits protective and therapeutic effect in the course of experimental pancreatitis. The aim of present study was to examine the role of GH and insulin-like growth factor-1 (IGF-1) in these effects. Acute pancreatitis was induced by cerulein. Study was performed on pituitary-intact hypophysectomized rats. Ghrelin was administered twice a day at the dose of 8 nmol/kg/dose. IGF-1 was given twice a day at the dose of 20 nmol/kg/dose. The severity of acute pancreatitis was assessed 0 h or 1, 2, 3, 5 and 10 days after the last dose of cerulein. Administration of cerulein led to the development of acute edematous pancreatitis. In pituitary-intact rats, treatment with ghrelin reduced biochemical indexes of the severity of acute pancreatitis and morphological signs of pancreatic damage, leading to faster regeneration of the pancreas reduction in serum concentration of pro-inflammatory interleukin-1β and decrease in serum activity of amylase and lipase. These effects were accompanied with an improvement of pancreatic blood flow and an increase in pancreatic DNA synthesis. Hypophysectomy delayed the healing of the pancreas and abolished the therapeutic effect of ghrelin. In hypophysectomized rats with pancreatitis, treatment with IGF-1 exhibits therapeutic effect similar to that observed in ghrelin-treated rats with the intact pituitary. We conclude that therapeutic effect of ghrelin in cerulein-induced pancreatitis is indirect and depends on the release of GH and IGF-1.

摘要

胃饥饿素是生长激素促分泌素受体的配体,可刺激生长激素(GH)的释放。最近的研究表明,胃饥饿素治疗在实验性胰腺炎的过程中具有保护和治疗作用。本研究的目的是研究 GH 和胰岛素样生长因子-1(IGF-1)在这些作用中的作用。通过胆胰管收缩素诱导急性胰腺炎。在垂体完整的垂体切除大鼠中进行了研究。每天两次给予胃饥饿素,剂量为 8 nmol/kg/剂量。每天两次给予 IGF-1,剂量为 20 nmol/kg/剂量。在最后一次胆胰管收缩素给药后 0 小时或 1、2、3、5 和 10 天评估急性胰腺炎的严重程度。胆胰管收缩素给药导致急性水肿性胰腺炎的发展。在垂体完整的大鼠中,胃饥饿素治疗可降低急性胰腺炎严重程度的生化指标和胰腺损伤的形态学迹象,导致胰腺更快再生,血清促炎白细胞介素-1β浓度降低,血清淀粉酶和脂肪酶活性降低。这些作用伴随着胰腺血流的改善和胰腺 DNA 合成的增加。垂体切除术延迟了胰腺的愈合,并消除了胃饥饿素的治疗作用。在患有胰腺炎的垂体切除大鼠中,IGF-1 治疗具有与垂体完整的胃饥饿素治疗大鼠观察到的相似的治疗作用。我们得出结论,胃饥饿素在胆胰管收缩素诱导的胰腺炎中的治疗作用是间接的,取决于 GH 和 IGF-1 的释放。

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