Stringer Andrea M, Gibson Rachel J, Bowen Joanne M, Logan Richard M, Ashton Kimberly, Yeoh Ann S J, Al-Dasooqi Noor, Keefe Dorothy M K
Department of Medical Oncology, Royal Adelaide Hospital, South Australia, Australia.
Int J Exp Pathol. 2009 Oct;90(5):489-99. doi: 10.1111/j.1365-2613.2009.00671.x.
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 beta-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 beta-glucuronidase was detected. In conclusion, irinotecan-induced diarrhoea may be caused by an increase in some beta-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.
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所致。伊立替康与严重的粘膜炎和腹泻有关，其机制仍知之甚少。细菌β-葡萄糖醛酸酶被认为参与伊立替康的代谢，这表明肠道菌群与之相关。肠道粘蛋白也可能与化疗引起的腹泻的发生有关。给大鼠注射200mg/kg的伊立替康，并在96、120和144小时处死。监测大鼠的腹泻情况。进行病理学和免疫组织化学染色。对样本进行培养，并使用实时聚合酶链反应分析粪便DNA。在72至96小时观察到严重腹泻。治疗后还观察到体重下降。在小肠和大肠中观察到杯状细胞数量（完整细胞和空泡化细胞）有显著变化。仅在小肠中观察到MUC基因表达的变化。观察到肠道菌群谱的改变，尤其是大肠杆菌，并且检测到β-葡萄糖醛酸酶的表达增加。总之，伊立替康引起的腹泻可能是由一些产生β-葡萄糖醛酸酶的细菌，尤其是大肠杆菌的增加所致，这加剧了活性代谢产物的毒性。粘液分泌和粘蛋白释放加速也可能导致腹泻延迟发作。
