Development of an animal model of chronic alcohol-induced pancreatitis in the rat
Development of an animal model of chronic alcohol-induced pancreatitis in the rat
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DOI：
10.1152/ajpgi.2001.280.6.g1178
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发表时间：
2001-06-01
影响因子：
4.5
通讯作者：
Thurman, RG
中科院分区：
文献类型：
--
作者：
Kono, H;Nakagami, M;Thurman, RG
本研究旨在开发酒精性胰腺炎的动物模型，并检验乙醇剂量和膳食脂肪类型影响自由基形成和胰腺病理学的假设。雌性 Wistar 大鼠经肠饲喂富含玉米油（不饱和脂肪）的流质饮食，有或没有标准或高剂量的乙醇，以及中链甘油三酯（饱和脂肪）和高剂量的乙醇，持续 8 周。随着耐受性的发展，乙醇的剂量增加，这使得高剂量组输送的酒精量大约是高剂量组的两倍。富含不饱和脂肪的饮食（含或不含标准剂量的乙醇）4周后，血清胰酶和组织学均正常。相反，高剂量乙醇显着升高酶水平。饮食中的饱和脂肪显着抑制了增加。肠内乙醇喂养 4 周后，胰腺中未检测到纤维化和胶原蛋白 α1(I) 表达；然而，8周后高剂量的效果显着增强。此外，在标准剂量下，通过电子自旋共振检测到的自由基加合物极少；然而，高剂量显着增加了碳中心自由基加合物以及 4-羟基壬烯醛（脂质过氧化指数）。饮食中的饱和脂肪也会使自由基加合物减弱约 70%。这里介绍的动物模型是第一个以可重复的方式证明慢性酒精诱发的胰腺炎的动物模型。造成病理学的关键因素是乙醇的摄入量和膳食脂肪的类型。
This study was designed to develop an animal model of alcoholic pancreatitis and to test the hypothesis that the dose of ethanol and the type of dietary fat affect free radical formation and pancreatic pathology. Female Wistar rats were fed liquid diets rich in corn oil (unsaturated fat), with or without a standard or high dose of ethanol, and medium-chain triglycerides (saturated fat) with a high dose of ethanol for 8 wk enterally. The dose of ethanol was increased as tolerance developed, which allowed approximately twice as much alcohol to be delivered in the high-dose group. Serum pancreatic enzymes and histology were normal after 4 wk of diets rich in unsaturated fat, with or without the standard dose of ethanol. In contrast, enzyme levels were elevated significantly by the high ethanol dose. Increases were blunted significantly by dietary saturated fat. Fibrosis and collagen alpha1(I) expression in the pancreas were not detectable after 4 wk of enteral ethanol feeding; however, they were enhanced significantly by the high dose after 8 wk. Furthermore, radical adducts detected by electron spin resonance were minimal with the standard dose; however, the high dose increased carbon-centered radical adducts as well as 4-hydroxynonenal, an index of lipid peroxidation, significantly. Radical adducts were also blunted by similar to 70% by dietary saturated fat. The animal model presented here is the first to demonstrate chronic alcohol-induced pancreatitis in a reproducible manner. The key factors responsible for pathology are the amount of ethanol administered and the type of dietary fat.