Pandol S J, Periskic S, Gukovsky I, Zaninovic V, Jung Y, Zong Y, Solomon T E, Gukovskaya A S, Tsukamoto H
CURE: Digestive Diseases Research Center, Departments of Medicine, Veterans Affairs Greater Los Angeles Healthcare System and University of California, Los Angeles, California, USA.
Gastroenterology. 1999 Sep;117(3):706-16. doi: 10.1016/s0016-5085(99)70465-8.
BACKGROUND & AIMS: Although alcoholism is a major cause of pancreatitis, the pathogenesis of this disorder remains obscure. Failure to produce experimental alcoholic pancreatitis suggests that ethanol may only increase predisposition to pancreatitis. This study sought to develop a model of ethanol pancreatitis by determining if an ethanol diet sensitizes rats to pancreatitis caused by cholecystokinin octapeptide (CCK-8).
Rats were fed intragastrically either control or ethanol diet for 2 or 6 weeks. The animals were then infused for 6 hours with either saline or CCK-8 at a dose of 3000 pmol. kg(-1). h(-1), which by itself did not induce pancreatitis. The following parameters were measured: serum amylase and lipase levels, pancreatic weight, inflammatory infiltration, number of apoptotic acinar cells, pancreatic messenger RNA (mRNA) expression of cytokines and chemokines, and nuclear factor (NF)-kappaB activity.
All measures of pancreatitis, as well as NF-kappaB activity and mRNA expression for tumor necrosis factor alpha, interleukin 6, monocyte chemotactic protein 1, macrophage inflammatory protein 2, and inducible nitric oxide synthase, were significantly increased only in rats treated with ethanol plus CCK-8.
An ethanol diet sensitizes rats to pancreatitis caused by CCK-8. The combined action of ethanol and CCK-8 results in NF-kappaB activation and up-regulation of proinflammatory cytokines and chemokines in the pancreas. These mechanisms may contribute to the development of alcoholic pancreatitis.
尽管酒精中毒是胰腺炎的主要病因，但这种疾病的发病机制仍不清楚。未能成功诱导出实验性酒精性胰腺炎表明乙醇可能只是增加了患胰腺炎的易感性。本研究旨在通过确定乙醇饮食是否使大鼠对由八肽胆囊收缩素（CCK-8）引起的胰腺炎敏感，来建立乙醇性胰腺炎模型。
给大鼠灌胃对照饮食或乙醇饮食2周或6周。然后给动物以3000 pmol·kg⁻¹·h⁻¹的剂量静脉输注生理盐水或CCK-8 6小时，该剂量本身不会诱发胰腺炎。测量以下参数：血清淀粉酶和脂肪酶水平、胰腺重量、炎症浸润、凋亡腺泡细胞数量、胰腺中细胞因子和趋化因子的信使核糖核酸（mRNA）表达以及核因子（NF）-κB活性。
仅在接受乙醇加CCK-8治疗的大鼠中，所有胰腺炎指标以及NF-κB活性和肿瘤坏死因子α、白细胞介素6、单核细胞趋化蛋白1、巨噬细胞炎性蛋白2和诱导型一氧化氮合酶的mRNA表达均显著增加。
乙醇饮食使大鼠对CCK-8引起的胰腺炎敏感。乙醇和CCK-8的联合作用导致胰腺中NF-κB活化以及促炎细胞因子和趋化因子上调。这些机制可能有助于酒精性胰腺炎的发展。
