Interleukin 1 receptor antagonist reduces lethality and intestinal toxicity of 5-fluorouracil in a mouse mucositis model.
Interleukin 1 receptor antagonist reduces lethality and intestinal toxicity of 5-fluorouracil in a mouse mucositis model.
复制标题
DOI：
10.1016/j.biopha.2010.06.006
复制
发表时间：
2010-11
期刊：
影响因子：
--
通讯作者：
Zhenqian Wu;Xiao-dong Han;S. Qin;Qi Zheng;Zhi-gang Wang;Di Xiang;Jing Zhang;Huili Lu;Mingyuan Wu;Shunying Zhu;Yan Yu;Yu Wang;W. Han
中科院分区：
文献类型：
--
作者：
Zhenqian Wu;Xiao-dong Han;S. Qin;Qi Zheng;Zhi-gang Wang;Di Xiang;Jing Zhang;Huili Lu;Mingyuan Wu;Shunying Zhu;Yan Yu;Yu Wang;W. Han
化疗引起的肠粘膜炎仍然是一个未解决的医学问题。5-采用化疗药物氟尿嘧啶（5-Fu）建立粘膜炎动物模型。应用全基因表达谱芯片技术研究与粘膜炎发病相关的基因信号。白细胞介素1受体拮抗剂（IL-1 Ra）是具有特征性基因表达谱的候选基因之一。其时间表达模式与小鼠小肠单次注射5-Fu后的损伤和再生阶段相关。重组IL-1 Ra对5-Fu诱导的小鼠肠粘膜炎模型有明显的治疗作用。IL-1 Ra治疗降低了急性致死率，加速了体重恢复，并消除了严重腹泻。症状益处得到病理学益处的支持，其中用IL-1 Ra处理的小鼠的小肠结构完整性的损伤比用溶剂对照处理的小鼠的损伤小且恢复更快。为了将治疗剂提供给未满足的医疗条件，需要进一步研究IL-1 Ra在化疗诱导的肠粘膜炎中的作用机制和翻译。
Chemotherapy-induced intestinal mucositis is still an unmet medical problem. 5-Fluorouracil (5-Fu), a chemotherapy drug, was used to create the animal model of mucositis. Global gene expression array was applied to identify genetic signals involved in the pathogenesis of mucositis. Interleukin 1 receptor antagonist (IL-1Ra) was one of the candidates with the characteristic gene expression profile. Its temporal expression pattern correlated to the damage and regeneration phase of the small intestine after a single injection of 5-Fu to mice. Administration of recombinant IL-1Ra to the mouse model of intestinal mucositis induced by 5-Fu demonstrated its therapeutic effects to the symptoms and pathology of the disease. The IL-1Ra treatment reduced the acute lethality, accelerated their body weight recovery, and eliminated severe diarrhea. The symptomatic benefits were supported by the pathological benefits, in which the mice treated with IL-1Ra had less damage and faster recovery of the structure integrity of their small intestine than that of the mice treated with vehicle control. To deliver the therapeutics to the unmet medical condition, further mechanism and translational studies of IL-1Ra in the settings of chemotherapy-induced intestinal mucositis are warranted.