全肠外营养（TPN）作为临床重要的治疗手段，挽救了大量重症病人的生命，但TPN相关的肠屏障损伤是导致TPN并发症的重要原因，也限制了TPN的临床应用和疗效，其发病机理和防治研究进展缓慢。目前使用的TPN相关肠屏障损伤模型在正常动物中建立，既与临床实际不符又缺乏肠屏障损伤的全面评估机制。本项目率先在C57BL/6J小鼠上通过DSS诱导肠道损伤后进行TPN干预，在此基础上建立肠屏障损伤动物模型：①建立了稳定的TPN相关肠屏障损伤小鼠模型；②系统性观察TPN相关肠屏障损伤动物模型肠道的病理生理改变；③比较不同品系小鼠模型及人体标本TPN后肠屏障功能损伤差异，确定模型与临床的符合度；④应用该模型研究肠外营养相关肝脏、骨骼肌等远隔器官的病理生理改变及机制。本课题为TPN导致肠屏障损伤及器官功能障碍等的发病机制研究，防治策略制定及TPN临床合理应用提供模式动物平台，具有重要转化医学意义和广阔应用前景。

Total parenteral nutrition (TPN), as an important clinical treatment, has saved a large number of critically ill patients. But TPN associated intestinal barrier damage, which is one of the important reasons leading to TPN related complications, limits the clinical application and weakens the therapeutic effect of TPN. By now, the research progress related pathogenesis and prevention strategy has been limited. Currently, most of the TPN related intestinal barrier damage models are made in normal animals which are not only inconsistent with clinical practice but also lack of comprehensive mechanism evaluation about intestinal barrier damage. This project took the lead to adopt C57BL/6J mice after intestinal injury induced by DSS to establish TPN associated intestinal barrier damage mice model: (1) to build a solid TPN associated intestinal barrier damage animal model; (2) to study the intestinal pathophysiology of the animal model systematically; (3) to compare the differences of intestinal barrier function after administering TPN between the different strain mice and human specimens, meanwhile, to determine whether the mouse model is in accordance with the clinical practice; (4) to study the intestinal pathophysiology and the related mechanism of the remote organs such as liver and skeletal muscle after administering parenteral nutrition in mice. This project will establish the animal model platform to study the mechanism of intestinal mucosa injury and organ dysfunction, to make the preventions and control strategies and to guide the clinical application of TPN in reasonable way. Therefore, this project will promote the progress of TPN associated intestinal barrier damage in the perspective of translational medicine and have broad application prospects.