化疗引起肠黏膜损伤出现严重消化道副作用，限制了药物剂量和疗程而影响疗效的发挥，但对化疗引起肠损伤的机制至今尚不清楚，尤其对于肠神经和肠干细胞在此过程中的作用，现在研究资料报道甚少。我们前期的研究工作发现阻断交感神经可显著减少肠道干细胞的数量，也发现5-FU化疗后不仅对肠粘膜形态及干细胞造成损伤，且肠交感神经活性降低、酪氨酸羟化酶表达减少，表明肠神经和肠干细胞在化疗消化道损伤和修复过程中具有一定作用。为此，本项目拟借助5-FU化疗肠损伤小鼠模型、ADRB2基因敲除模型和体外肠道干细胞培养模型，应用组织病理学、分子生物学、体视学和基因芯片技术探索生理和病理状态下肠道交感神经与肠道干细胞的相关关系；探索拟交感胺类药异丙肾上腺素对化疗后肠道干细胞损伤的保护作用与分子机制；并进一步研究脑源性神经营养因子4甲基儿茶酚对肠道干细胞损伤的保护作用，为寻找预防及治疗化疗引起的胃肠道综合征提供新思路与新方法。

Chemotherapy-induced intestinal mucosal injury has severe gastrointestinal side effects, which limits the dosage and course of the treatment and affects the effectiveness of the treatment. However, the mechanism of intestinal injury caused by chemotherapy is still unknown. Particularly, there are rare studies to investigate the role of intestinal nerve and stem cells under chemotherapy. Our previous data indicate that blocking sympathetic nerve could significantly reduce the number of intestinal stem cells. It was also found that 5-FU chemotherapy not only damaged intestinal mucosal and stem cells, but also reduced intestinal sympathetic nerve activity and tyrosine hydroxylase expression, indicating that intestinal nerve and stem cells play a crucial role in the gastrointestinal injury after chemotherapy. To this end, this current project intends to explore the relationship between intestinal sympathetic nerve and intestinal stem cells in physiological and pathological conditions via 5-FU chemotherapy-induced intestinal injury model, ADRB2 gene knockout mice model and intestinal stem cell culture model in vitro. Using histopathology, molecular biology, stereology and gene chip technology, the effects of sympathomimetic amines isoprenaline on intestinal stem cells were investigated after chemotherapy. The protective effects of brain-derived neurotrophic factor 4-methyl catechol on intestinal stem cell injury were further explored. The proposal will provide new ideas and new methods for the prevention and treatment of gastrointestinal syndrome induced by chemotherapy.