放射性肠损伤后小肠干细胞再生的研究与进展

摘要

BACKGROUND:Radiation-induced intestinal injury causes a sharp reduction in the number of intestinal stem cells (ISCs) and their dysfunction.This brings great challenges in the repair of injured intestinal epithelium.Prompting restoration of the number and function of ISCs is a highlight of current research in the treatment of radiation-induced intestinal injury as well as in the repair of injured intestinal epithelium.OBJECTIVE:To review the latest progress in the pathway and mechanism of ISCs replenishment after radiation-induced intestinal injury.METHODS:The first author searched the CNKI,Wanfang and PubMed databases using the keywords of “intestinal stem cell,radiation-induced intestinal injury” in Chinese and English,respectively,to retrieve relevant articles published from January 2010 to June 2016.Then we generalized and summarized the results of these articles.RESULTS AND CONCLUSION:The fate of ISCs is regulated by various signal pathways,mainly including Wnt/β-catenin,BMP,Notch and EGF pathways.Early secretory progenitors (ESPs) are relatively quiescent during homeostasis,and insensitive to radiation injury;moreover,the ESPs can convert to ISCs under certain conditions.So,they are desired source of “reserve stem cells”.Stem cell niche plays an important role in reverse differentiation from ESPs to ISCs,but the exact regulatory mechanism remains largely unknown.Investigation on the above mechanism is of important scientific significance for deeply understanding the restoration process after radiation-induced intestinal injury and thus actively regulating intestinal injury repair.%背景:放射性肠损伤造成小肠干细胞数量急剧减少和功能减退,导致损伤后的肠上皮修复非常困难,促进小肠干细胞数量和功能的恢复是当前治疗放射性肠损伤、修复受损肠上皮的研究热点.目的:综述放射性肠损伤后小肠干细胞补充来源及调控机制的最新研究进展.方法:分别以“小肠干细胞,放射性肠损伤;intestinal stem cell,radiation-induced intestinal injury”为检索词,由第一作者检索2010年1月至2016年6月中国期刊全文数据库、PubMed数据库及万方数据库相关文章,进行归纳总结.结果与结论:小肠干细胞的命运受多种信号通路的调控,研究比较明确的有Wnt/β-catenin、BMP、Notch和EGF信号通路.早期分泌型祖细胞在正常稳态下增殖缓慢,对放射性损伤不敏感,并且在一定条件下可重新逆转分化成为小肠干细胞,是“储备干细胞”的良好来源,而巢在早期分泌型祖细胞逆转分化为小肠干细胞的过程中发挥着重要作用.探究上述逆转分化过程的具体调控机制对于深入理解放射性肠损伤后肠上皮的修复过程,从而确立主动调控肠损伤修复的理念具有重要科学意义.