Department of Physiology, Jagiellonian University Medical College, Cracow, Poland.
J Physiol Pharmacol. 2010 Aug;61(4):419-27.
Recent studies have shown that pretreatment with ghrelin exhibits protective effect in the gut. Administration of ghrelin reduces gastric mucosal damage, as well as inhibits the development of experimental pancreatitis. However, this protective effect requires administration of ghrelin before gastric or pancreatic damage and thus has a limited clinical value. The aim of present study was to assess the influence of ghrelin administered after development of acute pancreatitis on the course of this disease. Acute pancreatitis was induced by cerulein. Ghrelin was administered twice a day for 1, 2, 4, 6 or 9 days at the dose of 4, 8 or 16 nmol/kg/dose. The first dose of ghrelin was given 24 hours after last injection of cerulein. The severity of acute pancreatitis was assessed between 0 h and 10 days after cessation of cerulein administration. Administration of caerulein led to the development of acute edematous pancreatitis and maximal severity of this disease was observed 24 hours after induction of pancreatitis. Treatment with ghrelin reduced morphological signs of pancreatic damage such as pancreatic edema, leukocyte infiltration and vacuolization of acinar cells, and led to earlier regeneration of the pancreas. Also biochemical indexes of the severity of acute pancreatitis, serum activity of lipase and amylase were significantly reduced in animals treated with ghrelin. These effects were accompanied by an increase in the pancreatic DNA synthesis and a decrease in serum level of pro-inflammatory interleukin-1b. Administration of ghrelin improved pancreatic blood flow in rats with acute pancreatitis. We conclude that: (1) treatment with ghrelin exhibits therapeutic effect in caerulein-induced experimental acute pancreatitis; (2) this effect is related, at least in part, to the improvement of pancreatic blood flow, reduction in proinflammatory interleukin-1beta and stimulation of pancreatic cell proliferation.
最近的研究表明,ghrelin 的预处理在肠道中表现出保护作用。给予 ghrelin 可减少胃黏膜损伤,并抑制实验性胰腺炎的发展。然而,这种保护作用需要在胃或胰腺损伤之前给予 ghrelin,因此临床价值有限。本研究旨在评估急性胰腺炎发生后给予 ghrelin 对疾病进程的影响。通过 Cerulein 诱导急性胰腺炎。ghrelin 以 4、8 或 16 nmol/kg/剂量每天两次给药,共 1、2、4、6 或 9 天。ghrelin 的第一剂在最后一次 Cerulein 注射后 24 小时给予。在停止 Cerulein 给药后 0 h 至 10 天评估急性胰腺炎的严重程度。给予 Cerulein 导致急性水肿性胰腺炎的发展,并且在诱导胰腺炎后 24 小时观察到这种疾病的最大严重程度。ghrelin 的治疗减轻了胰腺损伤的形态学迹象,如胰腺水肿、白细胞浸润和腺泡细胞空泡化,并导致胰腺更早地再生。ghrelin 治疗还显著降低了急性胰腺炎严重程度的生化指标,如血清脂肪酶和淀粉酶活性。这些作用伴随着胰腺 DNA 合成的增加和促炎白细胞介素-1b 血清水平的降低。ghrelin 的给药改善了急性胰腺炎大鼠的胰腺血流。我们得出结论:(1)ghrelin 的治疗在 Cerulein 诱导的实验性急性胰腺炎中表现出治疗作用;(2)这种作用至少部分与改善胰腺血流、减少促炎白细胞介素-1b 和刺激胰腺细胞增殖有关。
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