L-瓜氨酸预处理有利于小鼠黏膜炎模型小肠黏膜结构和通透性

　　背景：黏膜炎是放疗和化疗患者的一种常见并发症。患者表现为疼痛、生活质量差、营养不良，从而引起住院次数增加和住院时间延长。使用免疫营养素或许可作为一种有利于改善临床结局的替代治疗选择。

　　目的：评估L-瓜氨酸（CIT）在5-氟尿嘧啶（5FU）所致黏膜炎小鼠模型中应用的作用。

　　方法：将Swiss雄性小鼠随机分为4组：对照组、CIT组、5FU组和5FU＋CIT组。给予小鼠商业饲料并补充丙氨酸口服溶液（对照和5FU组）或CIT（CIT和5FU＋CIT组）。在第7天，腹腔内给予小鼠磷酸盐缓冲液（PBS）或5FU（200mg/kg，单次给药）诱导黏膜炎。在第10天，处死小鼠，采集血标本和小肠标本。对小肠重量、形态、组织病理学评分（HE染色：0～12分）、过氧化物酶活性、氧化应激水平以及肠道通透性进行分析。

　　结果：治疗组和对照组在给予5FU后，小肠重量均明显减轻，CIT应用有助于黏膜结构部分恢复、组织病理学评分下降、肠道通透性部分恢复。

　　结论：使用CIT可以减轻5FU所致小肠黏膜结构损伤，减少损伤面积并促进肠道通透性增加。

JPEN J Parenter Enteral Nutr. 2016;40(2):279-86.

Pretreatment With L-Citrulline Positively Affects the Mucosal Architecture and Permeability of the Small Intestine in a Murine Mucositis Model.

Antunes MM, Leocádio PC, Teixeira LG, Leonel AJ, Cara DC, Menezes GB, Generoso Sde V, Cardoso VN, Alvarez-Leite JI, Correia MI.

Universidade Federal de Minas Gerais, Belo Horizonte-MG, Brazil; Universidade Federal de Lavras, Lavras-MG, Brazil.

BACKGROUND: Mucositis is a common complication in patients undergoing radiotherapy and chemotherapy. It is associated with pain, poor quality of life, and malnutrition, leading to an increased number of hospital admissions and prolonged hospitalization. The use of immunonutrients may be an alternative treatment option, which may help to improve patient outcome.

OBJECTIVE: Here we assessed the impact of L-citrulline (CIT) on a murine model of 5-fluorouracil (5FU)-induced mucositis.

METHODS: Swiss male mice were randomized into 4 groups: control, CIT, 5FU, and 5FU+CIT. Mice were fed with commercial chow and supplemented with an oral solution of alanine (control and 5FU groups) or CIT (CIT and 5FU+CIT groups). On the seventh day, mice received intraperitoneal phosphate-buffered saline or 5FU (200 mg/kg, single dose) to induce mucositis. On the 10th day, mice were euthanized, and the blood and small intestines were harvested. Body weight, morphology, histopathology score (hematoxylin and eosin) of the small intestine (from 0-12), myeloperoxidase activity, oxidative stress level, and intestinal permeability were assessed.

RESULTS: We observed significant weight loss after the administration of 5FU in both treated and control animals. CIT administration contributed to a partial recovery of the mucosal architecture as well as an intermediate reduction of the histopathologic score, and functional intestinal permeability was partially rescued.

CONCLUSIONS: CIT administration attenuated 5FU-mediated damage to the mucosal architecture of the small intestine, decreasing the size of the injured areas and promoting decreased intestinal permeability.

KEYWORDS: 5FU; L-citrulline; intestinal permeability; mucositis

PMID: 25573703

DOI: 10.1177/0148607114567508