Guangyao Li,1– 3,* Binghui Jin,3,* Jialin Zhou,3,* Tao Sun,1 Shuang Wang,4 Zhe Fan2,3 

1Department of Oncology, Cancer Hospital of Dalian University of Technology, Shenyang, People’s Republic of China; 2Department of General Surgery, Dalian Third People’s Hospital Affiliated to Dalian University of Technology, Dalian, People’s Republic of China; 3Department of General Surgery, The Third People’s Hospital of Dalian, Dalian Medical University, Dalian, People’s Republic of China; 4Department of Endocrinology, The Second Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Zhe Fan, Email fanzhe1982@hotmail.com Shuang Wang, Email wangshuang1986721@163.com

Abstract: Intestinal ischemia-reperfusion (II/R) injury is a common perioperative complication that occurs during severe infections, trauma, and multiple surgical procedures. II/R not only leads to localized intestinal damage but also disrupts the intestinal mucosal barrier, inducing systemic inflammatory responses and multi-organ failure, especially acute lung injury (ALI). The mechanisms are complex, involving multiple pathological processes such as oxidative stress, systemic inflammatory response, apoptosis, autophagy, and ferroptosis. During II/R, the large amount of reactive oxygen species and inflammatory factors produced rapidly activates immune cells and destroys the alveolar barrier, leading to pulmonary edema and hypoxemia, and in severe cases, acute respiratory distress syndrome (ARDS) may develop, ultimately causing respiratory failure. Current treatments include anti-inflammatory, antioxidant and anti-apoptotic drugs, as well as surgical interventions and traditional Chinese medicine. However, these methods have high drug toxicity and limited efficacy. With the development of nanomedicine, new strategies have emerged for the treatment of II/R-ALI. Nanomedicines, owing to their excellent bioavailability and targeting capabilities, can significantly enhance therapeutic outcomes and reduce side effects. This review summarizes the major mechanisms underlying II/R-ALI and discusses recent advances in the application of nanomaterials for its treatment.

Keywords: intestinal ischemia-reperfusion, acute lung injury, pathogenesis, nanomedicine, therapeutic strategies