IL-1β活化脂肪间充质干细胞对小肠缺血再灌注损伤的修复作用及机制研究

项目名称： IL-1β活化脂肪间充质干细胞对小肠缺血再灌注损伤的修复作用及机制研究

项目编号： No.81501601

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 刘流

作者单位： 安徽医科大学

项目金额： 18万元

中文摘要： 小肠缺血再灌注(IR)损伤在危重疾病(如创伤和休克)中十分常见；促进小肠IR损伤的愈合显著降低危重疾病并发症的发生率和死亡率。小肠IR损伤的病理生理特征为氧自由释放、炎症反应、细胞凋亡和微循环障碍。我们的前期研究结果提示脂肪间充质干细胞(ADMSC)抑制炎症反应、改善微循环和促进消化道组织再生；其机制为ADMSC通过上调表达COX-2-PGE2信号通路而发挥作用。ADMSC活化是其抑制炎症和促进组织再生的前提；目前，少数研究提示体外活化ADMSC能显著增强其组织修复能力。我们的预实验提示IL-1β体外活化ADMSC能够显著上调COX-2-PGE2信号通路的表达；因此，我们预测IL-1β活化的ADMSC通过上调表达COX-2-PGE2而促进小肠IR损伤的修复。本课题拟通过动物和细胞实验评价IL-1β体外活化ADMSC促进小肠IR损伤修复的作用，并探讨与COX-2-PGE2信号通路的内在关联。

中文关键词： 脂肪间充质干细胞；小肠缺血再灌注损伤；炎症反应；组织再生；分子机制

英文摘要： Intestinal ischemia-reperfusion (IR) injury is very common in a variety of critical diseases like trauma and shock; promoting the healing of intestinal IR injury will decrease the morbidity and mortality. Pathological features of intestinal IR injury include release of oxygen free radicals, excessive inflammatory reaction, cellular apoptosis and microcirculatory disturbance. Our previous studies indicated that adipose tissue-derived mesenchymal stem cells (ADMSC) suppress inflammatory reaction, improve blood supply and promote gut tissue regeneration, which are realized by upregulation of the expression of COX-2-PGE2 signaling pathway. Activation is the prerequisite for ADMSC to suppress inflammation and promote tissue regeneration, and a few studies have indicated that ADMSC was functional ascribed to its in vivo activation. Our preliminary data suggest that ADMSC significantly upregulate the expression of COX-2-PGE2 signaling with the in vitro stimulation of IL-1β. We hypothesize that activated ADMSC by IL-1β will promote the healing of intestinal IR injury through upregulation of the expression of COX-2-PGE2 signaling. This project will evaluate whether IL-1β-activated ADMSC promote the healing of intestinal IR injury, and we also explore the role of COX-2-PGE2 signaling in IL-1β-activated ADMSC for promotion of the healing of intestinal IR injury.

英文关键词： adipose tissue-derived mesenchymal stem cells;intestinal ischemia-reperfusion injury;inflammation;tissue regeneration;molecular mechanism