Irinotecan‐induced mucositis manifesting as diarrhoea corresponds with an amended intestinal flora and mucin profile
Irinotecan‐induced mucositis manifesting as diarrhoea corresponds with an amended intestinal flora and mucin profile
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DOI：
10.1111/j.1365-2613.2009.00671.x
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发表时间：
2009-10
影响因子：
3
通讯作者：
A. Stringer;R. Gibson;J. Bowen;Richard M. Logan;K. Ashton;A. Yeoh;Noor Al-dasooqi;D. Keefe
中科院分区：
文献类型：
--
作者：
A. Stringer;R. Gibson;J. Bowen;Richard M. Logan;K. Ashton;A. Yeoh;Noor Al-dasooqi;D. Keefe
化疗引起的腹泻是一个主要的肿瘤学问题，由癌症化疗的细胞毒性作用引起。伊立替康与重度粘膜炎和腹泻有关，其机制仍不清楚。认为细菌β-葡萄糖醛酸苷酶参与伊立替康的代谢，涉及肠道植物群。肠粘蛋白也可能与化疗诱导的腹泻有关。大鼠接受200 mg/kg伊立替康给药，并在96、120和144 h处死。监测大鼠的腹泻情况。病理组织学检查及免疫组化染色。培养样本，并使用真实的实时聚合酶链反应分析粪便DNA。从72至96 h观察到重度腹泻。治疗后还观察到体重减轻。在小肠和大肠中观察到杯状细胞数量（完整细胞和空化细胞）的显著变化。仅在小肠中观察到MUC基因表达的变化。观察到肠道植物群特征发生改变，尤其是大肠埃希菌，并检测到β-葡萄糖醛酸苷酶表达增加。总之，伊立替康诱导的腹泻可能是由某些产β-葡萄糖醛酸酶细菌（尤其是大肠埃希菌）增加引起的。大肠杆菌，加剧活性代谢物的毒性。粘液分泌加速和粘蛋白释放也可能导致腹泻延迟发作。
Chemotherapy‐induced diarrhoea is a major oncological problem, caused by the cytotoxic effects of cancer chemotherapy. Irinotecan is linked with severe mucositis and diarrhoea, the mechanisms of which remain poorly understood. Bacterial β‐glucuronidase is thought to be involved in the metabolism of irinotecan, implicating the intestinal flora. Intestinal mucins may also be implicated in the development of chemotherapy‐induced diarrhoea. Rats were treated with 200 mg/kg of irinotecan and killed at 96, 120 and 144 h. The rats were monitored for diarrhoea. Pathology and immunohistochemical staining was performed. The samples were cultured and faecal DNA was analysed using real‐time polymerase chain reaction. Severe diarrhoea was observed from 72 to 96 h. A decrease in body mass was also observed after treatment. Significant changes in goblet cell numbers (both complete and cavitated cells) were observed in the small and large intestines. Changes in MUC gene expression were observed in the small intestine only. Modifications were observed to the intestinal flora profile, especially Escherichia coli, and an increase in the expression of β‐glucuronidase was detected. In conclusion, irinotecan‐induced diarrhoea may be caused by an increase in some β‐glucuronidase‐producing bacteria, especially E. coli, exacerbating the toxicity of active metabolites. Accelerated mucous secretion and mucin release may also contribute to the delayed onset of diarrhoea.