Ethanol diet increases the sensitivity of rats to pancreatitis induced by cholecystokinin octapeptide
Ethanol diet increases the sensitivity of rats to pancreatitis induced by cholecystokinin octapeptide
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DOI：
10.1016/s0016-5085(99)70465-8
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发表时间：
1999-09-01
期刊：
影响因子：
29.4
通讯作者：
Tsukamoto, H
中科院分区：
文献类型：
--
作者：
Pandol, SJ;Periskic, S;Tsukamoto, H
背景与目的：虽然酒精中毒是胰腺炎的主要原因，但其发病机制尚不清楚。未能产生实验性酒精性胰腺炎表明乙醇可能只会增加胰腺炎的易感性。本研究试图通过确定乙醇饮食是否使大鼠对胆囊收缩素八肽（CCK-8）引起的胰腺炎敏感来建立乙醇性胰腺炎模型。方法：大鼠分别灌胃对照组和乙醇饲料2周和6周。然后给这些动物注射3000 pmol的生理盐水或CCK-8 6小时。公斤(1)。H(-1)，其本身不会诱发胰腺炎。测定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、胰腺细胞因子和趋化因子mRNA表达、核因子κ B活性。结果：仅在乙醇加CCK-8处理的大鼠中，胰腺炎的所有指标以及NF-kappa B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、巨噬细胞炎症蛋白2和诱导型一氧化氮合酶的mRNA表达均显著升高。结论：乙醇饮食对CCK-8引起的胰腺炎有增敏作用。乙醇和CCK-8的联合作用导致胰腺NF-kappa B的激活和促炎细胞因子和趋化因子的上调。这些机制可能有助于酒精性胰腺炎的发展。
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). Methods: 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)-kappa B activity. Results: All measures of pancreatitis, as well as NF-kappa B 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. Conclusions: An ethanol diet sensitizes rats to pancreatitis caused by CCK-8. The combined action of ethanol and CCK-8 results in NF-kappa B activation and up-regulation of proinflammatory cytokines and chemokines in the pancreas. These mechanisms may contribute to the development of alcoholic pancreatitis.