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封面故事:芦荟植物叶中的芦荟素可诱导 F344/N 雄性大鼠大肠的病理变化,并调节其微生物组成。

From the Cover: Aloin, a Component of the Aloe Vera Plant Leaf, Induces Pathological Changes and Modulates the Composition of Microbiota in the Large Intestines of F344/N Male Rats.

机构信息

Division of Biochemical Toxicology.

Toxicologic Pathology Associates, Inc., Jefferson Laboratories, Jefferson, Arkansas.

出版信息

Toxicol Sci. 2017 Aug 1;158(2):302-318. doi: 10.1093/toxsci/kfx105.

Abstract

In a previous study, the oral administration of an Aloe vera whole leaf extract induced dose-related mucosal and goblet cell hyperplasia in the rat colon after 13 weeks and colon cancer after 2 years. The primary goal of this study was to determine whether or not the administration of aloin, a component of the Aloe vera plant leaf, would replicate the pathophysiological effects that were observed in rats in the previous study with an Aloe vera whole leaf extract. Groups of 10 male F344/N rats were administered aloin at 0, 6.95, 13.9, 27.8, 55.7, 111, 223, and 446 mg/kg drinking water for 13 weeks. At the end of study, rat feces were collected, and the composition of fecal bacteria was investigated by next generation sequencing of the PCR-amplified V3/V4 region of the 16S rRNA gene. At necropsy, blood was collected by cardiac puncture and organs and sections of the large intestine were collected for histopathology. Aloin induced dose-related increased incidences and severities of mucosal and goblet cell hyperplasia that extended from the cecum to the rectum, with increased incidences and severities detected at aloin doses ≥55.7 mg/kg drinking water. Analysis of the 16S rRNA metagenomics sequencing data revealed marked shifts in the structure of the gut microbiota in aloin-treated rats at each taxonomic rank. This study highlights the similarities in effects observed for aloin and the Aloe vera whole leaf extract, and points to a potential mechanism of action to explain the observed pathological changes via modulation of the gut microbiota composition.

摘要

在之前的一项研究中,口服库拉索芦荟全叶提取物后,大鼠结肠在 13 周后出现剂量相关性黏膜和杯状细胞增生,并在 2 年后发生结肠癌。本研究的主要目的是确定芦荟素(芦荟植物叶的成分)的给药是否会复制之前用芦荟全叶提取物进行的大鼠研究中观察到的病理生理效应。10 只雄性 F344/N 大鼠分为 6.95、13.9、27.8、55.7、111、223、446mg/kg 组,连续 13 周灌胃给予芦荟素。研究结束时,收集大鼠粪便,通过聚合酶链反应扩增的 16S rRNA 基因 V3/V4 区的下一代测序来研究粪便细菌的组成。解剖时,通过心脏穿刺采集血液,并采集大肠的器官和切片进行组织病理学检查。芦荟素诱导了剂量相关性的黏膜和杯状细胞增生,其严重程度从盲肠延伸至直肠,在 55.7mg/kg 以上剂量的芦荟素灌胃时,增生的发生率和严重程度增加。16S rRNA 宏基因组测序数据分析显示,在每个分类等级上,芦荟素处理的大鼠肠道微生物群结构都发生了明显的变化。本研究强调了芦荟素和芦荟全叶提取物观察到的效应的相似性,并指出了一种潜在的作用机制,通过调节肠道微生物群组成来解释观察到的病理变化。

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