尾吊模拟失重效应对小鼠结肠上皮的影响和机制研究

航天飞行所带来的失重和多种应激可导致航天员骨肌系统和免疫系统发生多种改变，但对肠道粘膜组织，包括肠上皮、菌群和肠相关淋巴组织的影响还不清楚。前期工作中我们利用小鼠尾吊模型模拟失重效应，发现尾吊2周时肠道免疫稳态发生改变，肠道菌群失调、肠炎易感性增加；而尾吊4周时则主要表现为结肠隐窝缩短，杯状细胞减少和菌群失调。基于此，本项目将从结肠上皮、粘膜免疫和肠道菌群三个方面以及三者的相互调节探讨尾吊致结肠杯状细胞减少的原因以及其对粘膜屏障功能和肠炎发展和转归的影响。研究结果将有助于深入理解肠粘膜稳态的调控机制，为评估中长期失重对航天员肠道粘膜的影响提供实验依据和可能的检测手段，并为航天飞行中肠粘膜组织稳态的维护提供新的思路。

Spaceflight, in particular, microgravity, changes the muscle, bone, and immune system in many aspects. But microgravity-related intestinal mucosal changes and its clinical significance have not been well studied. Using the hindlimb unloading (HU) mouse model to simulate the microgravity condition, we found that 2-week HU mice had impaired mucosal immune homeostasis, altered microbiota, and increased susceptibility to dextran sulfate sodium-induced colitis; whereas 4-week HU mice had reduced colonic crypt length and goblet cell numbers and altered microbiota. Based on these data, the current project is going to investigate the mechanisms of goblet cell reduction by studying the tripartite cross-regulation of colonic epithelium, mucosal immune system, and microflora. The clinical significance of HU-induced goblet cell reduction will be also investigated. The results from these mouse studies will provide insights into the effects of microgravity on human intestinal mucosa and facilitate the development of monitoring approaches and counter measures to maintain the intestinal homeostasis.