Gastrointestinal Microflora and Mucins May Play a Critical Role in the Development of 5-Fluorouracil-Induced Gastrointestinal Mucositis
Gastrointestinal Microflora and Mucins May Play a Critical Role in the Development of 5-Fluorouracil-Induced Gastrointestinal Mucositis
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DOI：
10.3181/0810-rm-301
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发表时间：
2009-04-01
影响因子：
3.2
通讯作者：
Keefe, Dorothy M. K.
中科院分区：
文献类型：
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作者：
Stringer, Andrea M.;Gibson, Rachel J.;Keefe, Dorothy M. K.
5-氟尿嘧啶（5-FU）是临床肿瘤学实践中常用的化疗药物。它的两个主要副作用是粘膜炎和腹泻。粘蛋白的结构提供粘膜保护，并通过提供附着位点和防止细菌过度生长和/或渗透来维持肠道植物群。本研究的目的是研究5-FU治疗后粘蛋白分泌和微生物区系的变化。雌性DA大鼠单次i. p.给予150 mg/kg剂量的5-FU。在处理后的不同时间点处死大鼠。对照组大鼠未接受治疗。收集空肠、结肠和粪便样品。使用标准微生物培养技术鉴定细菌，并使用实时PCR定量粪便样品中的细菌。还对杯状细胞和空泡杯状细胞（经历粘液胞吐）进行计数。使用Kruskal-Wallis检验进行统计分析，这是一种检验组中位数相等性的非参数方法。在用5-FU治疗后，我们显示梭菌属减少，乳杆菌属和链球菌属，以及埃希氏菌属（Escherichia spp.）在空肠里在结肠中，5-FU引起肠球菌属减少，乳杆菌属和链球菌属粪便样品的实时PCR显示乳酸杆菌的下降趋势。和拟杆菌属slop.，E.杆菌梭状芽孢杆菌显著增加（P < 0.05）。和葡萄球菌属（Staphylococcus spp.）在24小时。空肠中杯状细胞数量从24-72 h显著减少，空泡杯状细胞百分比显著增加。总之，5-FU处理引起大鼠肠道植物群和粘蛋白分泌的显著变化。这些变化可能导致全身效应，特别是可能促进化疗诱导的粘膜炎的发展。实验生物医学234：430-441，2009
5-Fluorouracil (5-FU) is a commonly used chemotherapy agent in clinical oncology practice. Two of its major side effects are mucositis and diarrhoea. The structure of mucins offers mucosal protection, and allows maintenance of intestinal flora by providing attachment sites and preventing bacterial over-growth and/or penetration. The aim of this study was to investigate changes in mucin secretion and microflora following treatment with 5-FU. Female DA rats were given a single 150 mg/kg i.p. dose of 5-FU. Rats were killed at various time points after treatment. Control rats received no treatment. Jejunum, colon and faecal samples were collected. Standard microbiological culture techniques were used to identify bacteria, and real-time PCR was used to quantify bacteria in faecal samples. Goblet cells and cavitated goblet cells (having undergone mucus exocytosis) were also counted. Statistical analysis was carried out using Kruskal-Wallis test, a non-parametric method of testing equality of group medians. Following treatment with 5-FU, we showed decreases in Clostridium spp., Lactobacillus spp. and Streptococcus spp., and an increase in Escherichia spp. in the jejunum. In the colon, 5-FU caused decreases in Enterococcus spp., Lactobacillus spp. and Streptococcus spp. Real-time PCR of faecal samples showed decreasing trends in Lactobacillus slop. and Bacteroides slop., and an increasing trend in E. coli. Significant increases (P < 0.05) were seen in Clostridium spp. and Staphylococcus spp. at 24 h. Goblet cell numbers decreased significantly in the jejunum from 24-72 h, with a significant increase in the percentage of cavitated goblet cells. In conclusion, 5-FU treatment causes significant changes in intestinal flora and mucin secretion in rats. These changes could result in systemic effects and, in particular, may contribute to the development of chemotherapy-induced mucositis. Exp Biol Med 234:430-441, 2009