大剂量电离辐射暴露引起的肠粘膜屏障破坏常导致患者死亡，重建干细胞微环境是放射损伤后肠道干细胞和肠上皮得以再生的重要基础。交感神经参与多种干细胞及其微环境的组成和调控，但交感神经对肠道干细胞微环境的调控作用尚不清楚。严重创伤可引起交感神经过度兴奋，进而造成肠粘膜缺血缺氧、肠上皮细胞凋亡和肠屏障功能破坏。最近本课题组发现肾上腺素和去甲肾上腺素可通过与肠上皮细胞表面的β2-肾上腺素受体（β2-AR）结合促进肠上皮细胞增殖，同时放射损伤后3天潘氏细胞内β2-AR表达水平显著增加，因此我们提出交感神经兴奋可通过作用于β2-AR调节潘氏细胞功能从而促进放射损伤后肠道干细胞微环境的修复与重建这一理论假说。本课题将运用转基因小鼠、流式分选、类器官体培养和RNA-Seq等技术方法验证该假说并寻找其具体作用机制。其研究结果将深化对肠道干细胞微环境调控的相关认识，并为胃肠道放射损救治提供潜在新靶点。

Large dose of ionizing radiation usually causes severe mucosa damage in gastrointestinal tract, which would result in high mortality of patients. The reestablishment of intestinal stem cell (ISC) niche is the basis for the regeneration of ISC and whole GI epithelium. In mammals, activation of sympathetic nervous system is involved in the regulation of many adult stem cells and their niche. However, it still remains unknown that how sympathetic nerve regulates the niche of ISC. Sympathetic nervous system is frequently over activated after severe trauma and stress, which causes hypoxia and ischemia of intestinal mucosa, apoptosis of epithelial cells, and finally the breakdown of intestinal barrier. Our group has evidenced that epinephrine (EPI) and norepinephrine (NE) can promote the proliferation of intestinal epithelial cells through binding to β2-adrenergic receptors (β2-AR), and the expression of β2-AR in Paneth cells was significantly increased at 3d after radiation. So we propose that activation of sympathetic nerve could improve the function of Paneth cells by binding to their β2-AR and facilitate the reestablishment of ISC niche. In this project, we would employ transgenic mice, FACS, enteroid culture and RNA-Seq to validate this hypothesis and the potential mechanism(s). The results of this project would give us a further insight into the function of sympathetic nerve in the maintenance of ISC niche, and provide us a new potential target for the treatment of radiation caused GI symptoms.