内质网应激与急性肺损伤恶化关联性的研究进展OA北大核心

Acute lung injury(ALI)is a disease that seriously threatens the lives and health of people globally.Its primary pathological features include damage to alveolar epithelial cells and pulmonary capillary endothelial cells,leading to diffuse interstitial pulmonary edema and alveolar edema,often accompanied by acute hypoxemic respiratory insufficiency.Endoplasmic reticulum stress(ERS)plays a crucial role in the occurrence and development of ALI.It exacerbates ALI through multiple pathways.In terms of apoptosis,key proteins such as glucose-regulated protein 78(GRP78),C/EBP homologous protein(CHOP),and caspase-12 promote the apoptosis of pulmonary vascular endothelial cells and alveolar epithelial cells,thus aggravating lung tissue damage.In terms of reactive oxygen species(ROS)metabolism,ERS induces massive ROS release with involvement of NADPH oxidase.ROS directly impair pulmonary endothelial cells,leading to fluid leakage and worsening lung injury.In terms of the inflammatory response,ERS activates neutrophils.The interaction between complement-derived C5a and C5aR on neutrophils induces ERS,thereby amplifying lung inflammation.In terms of the ferroptosis pathway,ERS exacerbates the ferroptosis in alveolar epithelial cells,mediated by interactions between Mfn-2 and IRE1-α.Therefore,targeted interventions against ERS,such as the use of chemical chaperones or specific signaling pathway inhibitors,may provide new directions for the treatment of ALI and improve the prognosis of the patients and their quality of life.This paper comprehensively investigates the association between ERS and ALI to elucidate the underlying pathogenesis,providing useful support for better prevention and clinical management of ALI.