Bukowczan Jakub, Warzecha Zygmunt, Ceranowicz Piotr, Kuśnierz-Cabala Beata, Tomaszewska Romana, Dembinski Artur
Department of Endocrinology and Diabetes Mellitus, Northumbria NHS Foundation Trust, Rake Lane, NE28 8NH North Shields, Tyne and Wear, United Kingdom.
Department of Physiology, Jagiellonian University Medical College, Krakow, Poland.
Eur J Pharmacol. 2015 Aug 5;760:113-21. doi: 10.1016/j.ejphar.2015.04.016. Epub 2015 Apr 23.
Obestatin, as ghrelin, has been originally extracted from the stomach, which remains its major source. Previous studies have shown that administration of obestatin exhibits protective and healing-promoting effects in several organs, including the stomach and kidney. In pancreas, pretreatment with obestatin inhibits the development of cerulein-induced acute pancreatitis and promotes survival of pancreatic beta cells and human islets. The aim of the present study was to check the universality of protective effect of obestatin in the pancreas. For this reason we investigated the influence of obestatin administration on the development of ischemia/reperfusion-induced pancreatitis. Acute pancreatitis was induced by pancreatic ischemia followed by reperfusion of the gland. Obestatin (4, 8 or 16 nmol/kg/dose) was administered intraperitoneally twice: 0.5h before exposure to ischemia, and 3h after the first injection. The effect of obestatin on the course of necrotizing pancreatitis was assessed after 6-h reperfusion, and included histological, functional, and biochemical analyses. Treatment with obestatin reduced morphological signs of pancreatic damage including edema, vacuolization of acinar cells, hemorrhages, acinar necrosis, and leukocyte infiltration of the gland. These effects were accompanied by an improvement of pancreatic DNA synthesis and superoxide dismutase activity, and a decrease in serum level of lipase and pro-inflammatory interleukin-1β. Moreover pretreatment with obestatin reduced myeloperoxidase activity and malondialdehyde concentration in pancreatic tissue of rats with acute pancreatitis.
Administration of obestatin inhibits the development of ischemia/reperfusion-induced acute pancreatitis. This observation, taken together with previous findings that obestatin protects the pancreas against cerulein-induced pancreatitis, indicates that protective effect of obestatin in the pancreas is universal and independent of the primary cause of acute pancreatitis.
与胃饥饿素一样，肥胖抑制素最初是从胃中提取的，胃仍是其主要来源。先前的研究表明，给予肥胖抑制素对包括胃和肾脏在内的多个器官具有保护和促进愈合的作用。在胰腺中，肥胖抑制素预处理可抑制雨蛙肽诱导的急性胰腺炎的发展，并促进胰腺β细胞和人胰岛的存活。本研究的目的是检验肥胖抑制素在胰腺中保护作用的普遍性。因此，我们研究了给予肥胖抑制素对缺血/再灌注诱导的胰腺炎发展的影响。急性胰腺炎通过胰腺缺血后再灌注诱发。肥胖抑制素（4、8或16 nmol/kg/剂量）腹腔注射两次：在缺血前0.5小时，以及第一次注射后3小时。在再灌注6小时后评估肥胖抑制素对坏死性胰腺炎病程的影响，包括组织学、功能和生化分析。肥胖抑制素治疗减轻了胰腺损伤的形态学表现，包括水肿、腺泡细胞空泡化、出血、腺泡坏死和腺体白细胞浸润。这些作用伴随着胰腺DNA合成和超氧化物歧化酶活性的改善，以及血清脂肪酶水平和促炎白细胞介素-1β的降低。此外，肥胖抑制素预处理降低了急性胰腺炎大鼠胰腺组织中的髓过氧化物酶活性和丙二醛浓度。
给予肥胖抑制素可抑制缺血/再灌注诱导的急性胰腺炎的发展。这一观察结果与先前发现的肥胖抑制素可保护胰腺免受雨蛙肽诱导的胰腺炎的结果相结合，表明肥胖抑制素在胰腺中的保护作用是普遍的，且独立于急性胰腺炎的主要病因。
