Therapeutic Effect of Obestatin in the Course of Cerulein-Induced Acute Pancreatitis

Therapeutic Effect of Obestatin in the Course of Cerulein-Induced Acute Pancreatitis
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DOI:
10.1097/mpa.0000000000000517
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发表时间:
2016-05-01
期刊:
影响因子:
2.9
通讯作者:
Dembinski, Artur
Dembinski, Artur
中科院分区:
医学4区
文献类型:
--
作者:
Bukowczan, Jakub;Cieszkowski, Jakub;Dembinski, Artur

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目的:本研究的目的是确定的影响,obestatin治疗的过程中雨蛙肽诱导pancreatitis.Methods:急性胰腺炎诱导雨蛙肽腹腔注射5次,间隔1小时,剂量为50 μ g/kg每剂量。Obestatin每天给药两次,每次剂量为8 nmol/kg,在最后一次注射雨蛙肽后24小时开始第一次给药。结果:雨蛙肽可诱导大鼠急性水肿性胰腺炎(AP)的发生,并在诱导后24 h达到最严重程度。用obestatin治疗减少了胰腺损伤的形态学体征(胰腺水肿、白细胞浸润、腺泡细胞空泡化)并导致胰腺更早再生。胰腺炎严重程度的生化指标,如血清胰腺消化酶活性,在用obestatin治疗的动物显着降低。这些作用伴随胰腺DNA合成增加和促炎性白细胞介素1 β血清水平降低。此外,管理obestatin改善胰腺血流量在大鼠AP。结论:外源性obestatin治疗AP的严重程度降低,加速胰腺的恢复。
Objective: The aim of this study was to determine the impact of obestatin therapy on the course of cerulein-induced pancreatitis.Methods: Acute pancreatitis was induced by cerulein given intraperitoneally 5 times with 1 hour intervals at the dose of 50 mu g/kg per dose. Obestatin was administered twice a day at the dose of 8 nmol/kg per dose, starting the first dose 24 hours after the last injection of cerulein. Severity of acute pancreatitis (AP) was examined at 0 hour or 1, 2, 3, 5, 7, and 10 days after the last injection of cerulein.Results: Administration of cerulein led to development of acute edematous pancreatitis in all rats, and maximal severity of this disease was observed 24 hours after induction of pancreatitis. Treatment with obestatin reduced morphological signs of pancreatic damage (pancreatic edema, leukocyte infiltration, vacuolization of acinar cells) and led to earlier regeneration of the pancreas. Biochemical indexes of severity of pancreatitis such as serum activity of pancreatic digestive enzymes were significantly reduced in animals treated with obestatin. These effects were accompanied by increase in pancreatic DNA synthesis and decrease in serum level of proinflammatory interleukin 1 beta. In addition, administration of obestatin improved pancreatic blood flow in rats with AP.Conclusions: Treatment with exogenous obestatin reduces severity of AP and accelerates pancreatic recovery.