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巴雷特食管饮食相关小鼠模型中早期出现的发病率:锌的问题?

Early morbidity encountered in the dietary-related mouse model of Barrett's esophagus: a question of zinc?

作者信息

Grotenhuis B A, Franken P F, Swinkels W J C, Boonstra A, van der Valk M A, van Lanschot J J B, Fodde R

机构信息

Department of Surgery,Pathology, andGastroenterology and Hepatology, Erasmus MC, Rotterdam, andDepartment of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.

出版信息

Dis Esophagus. 2011 Jul;24(5):371-3. doi: 10.1111/j.1442-2050.2010.01151.x. Epub 2010 Dec 17.

Abstract

Recently, a mouse model for Barrett's esophagus based on a zinc-deficient diet supplemented with deoxycholic bile acids has been published. The aim of this study was to attempt to reproduce these data and extend them by employing genetically modified mice and intraperitoneal iron supplementation. The study design encompassed six experimental groups (wild type, Apc-mutant and Smad4-mutant mice, with or without iron injections), with all animals fed with the zinc-deficient diet supplemented with deoxycholic bile acids. All treatments were started at 3-5 weeks of age (the majority [78%] at 5 weeks). Animals were scheduled for euthanasia at two distinct time points, namely at 3 and 6 months of age. All mice showed signs of considerable distress already 4 weeks after the start of the modified diets, and had to be euthanized before the first evaluation time point (mean age 9.3 weeks, range 5-15 weeks). No differences were observed between wild type and genetically modified mice, or between animals with or without iron supplementation. On histological examination, we could not detect any lesions (Barrett's esophagus-like or tumors) other than esophagitis. In the currently presented experimental settings, we were not able to reproduce the mouse model according to which Barrett's-like lesions could be detected in animals fed with the zinc-deficient diet supplemented with deoxycholic bile acids.

摘要

最近,一种基于缺锌饮食并补充脱氧胆酸的巴雷特食管小鼠模型已被发表。本研究的目的是尝试重现这些数据,并通过使用基因改造小鼠和腹腔内补充铁来扩展这些数据。研究设计包括六个实验组(野生型、Apc突变型和Smad4突变型小鼠,有或没有注射铁),所有动物均喂食缺锌饮食并补充脱氧胆酸。所有处理均在3 - 5周龄开始(大多数[78%]在5周龄)。动物计划在两个不同的时间点实施安乐死,即3个月和6个月龄时。在改良饮食开始后仅4周,所有小鼠就已表现出相当痛苦的迹象,并且不得不在第一个评估时间点之前实施安乐死(平均年龄9.3周,范围5 - 15周)。在野生型和基因改造小鼠之间,或在补充铁与未补充铁的动物之间未观察到差异。在组织学检查中,除了食管炎外,我们未检测到任何病变(巴雷特食管样病变或肿瘤)。在当前呈现的实验设置中,我们无法重现那种在喂食缺锌饮食并补充脱氧胆酸的动物中可检测到巴雷特样病变的小鼠模型。

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