Regulated programmed cell death in sepsis associated acute lung injury: From pathogenesis to therapy

Sepsis associated acute lung injury (SALI) is a common complication in patients with severe sepsis and a disease with high morbidity and mortality in ICU patients. The main mechanism of SALI is pulmonary hypoperfusion due to hypotension and shock caused by sepsis, which leads to ischemic necrosis of alveolar endothelial cells and eventually lung failure. At present, SALI therapy mainly includes antibiotic therapy, fluid resuscitation, transfusion products and vasoactive drugs, but these strategies are not satisfactory. Therefore, focusing on the role of different cell death patterns in SALI may help in the search for effective treatments. Understanding the molecular mechanisms of SALI and identifying pathways that inhibit lung cell death are critical to developing effective drug therapies to prevent the progression of SALI. Cell death is controlled by programmed cell death (PCD) pathways, including apoptosis, necroptosis, ferroptosis, pyroptosis and autophagy. There is growing evidence that PCD plays an important role in the pathogenesis of SALI, and inhibitors of various types of PCD represent a promising therapeutic strategy. Therefore, understanding the role and mechanism of PCD in SALI is conducive to our understanding of its pathological mechanism, and is of great significance for the treatment of SALI. In this article, we discuss recent advances in the role of PCD in SALI, show how different signaling pathways (such as NF-κB, PI3K/Akt, mTOR, and Nrf2) regulate PCD to regulate SALI development, and discuss the associations between various types of PCD. The aim is to explore the molecular mechanism behind SALI and to find new targets for SALI therapy.