Patients with severe pneumonia caused by novel coronavirus infection are often complicated with acute respiratory distress syndrome (ARDS), which has a high mortality. ARDS is characterized by diffuse alveolar damage, pulmonary edema, and hypoxemia. Mitochondria are prone to morphological and functional abnormalities under hypoxia and viral infection, which can lead to cell apoptosis and damage, severely impacting the disease progression. Mitochondria maintain homeostasis through fission and fusion. In ARDS, hypoxia leads to the phosphorylation of dynamin-related protein 1 (Drp1), triggering excessive mitochondrial fission and damaging the alveolar epithelial barrier. Animal experiments have shown that inhibiting this process can alleviate lung injury, providing a potential direction for treatment. The pathology of novel coronavirus infection-related ARDS is similar to that of typical ARDS but more severe. Viral infection and hypoxia disrupt the mitochondrial balance, causing fission and autophagy abnormalities, promoting oxidative stress and mitochondrial DNA (mtDNA) release, activating inflammasomes, inducing the expression of hypoxia-inducible factor-1α (HIF-1α), exacerbating viral infection, inflammation, and coagulation reactions, and resulting in multiple organ damage. Mechanical ventilation and glucocorticoids are commonly used in the treatment of novel coronavirus infection-related ARDS. Mechanical ventilation is likely to cause lung and diaphragm injuries and changes in mitochondrial dynamics, while the lung protective ventilation strategy can reduce the adverse effects. Glucocorticoids can regulate mitochondrial function and immune response and improve the patient's condition through multiple pathways. The mitochondrial dynamics imbalance in novel coronavirus infection-related ARDS is caused by hypoxia and viral proteins, leading to lung and multiple organ injuries. To clarify the pathophysiological mechanism of mitochondrial dynamics imbalance in novel coronavirus infection-related ARDS and explore effective strategies for regulating mitochondrial dynamics balance to treat this disease, so as to provide new treatment targets and methods for patients with novel coronavirus infection-related ARDS. The existing treatments have limitations. Future research needs to deeply study the mechanism of mitochondrial dysfunction, develop new therapies and regulatory strategies, and improve the treatment effect.
Humans ; Respiratory Distress Syndrome/etiology* ; COVID-19 ; Mitochondrial Dynamics ; Mitochondria/metabolism* ; DNA, Mitochondrial ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Dynamins ; SARS-CoV-2

Objective:To investigate the effect of persimmon leaf extract (PLE) on HEK293-APPswe transgenic cells (20E2).Methods:To determine whether the 20E2 cells model was successfully established,the level of Aβ1-40 in SH-SY5Y was detected and 20E2 cells(HEK293 cells stably expressing Swedish mutant APP)cultured in vivo by ELISA kit,and the expression of APP protein level was detected by Western blot.Cell viability was assayed by CCK-8 method and then selected the best concentration.Set groups:SH-SY5Y as normal control group (NC group),20E2 as model group (20E2 group),treating with PLE as treating group (20E2+PLE group).Reactive oxygen species (ROS) levels of each group were detected with DCFH-DA fluorescent probe.The extracellular level of Aβ1-42 were detected by ELISA kit.Cytoplasmic Nrf2,Nuclear Nri2,Whole-cell HO-1 were detected by Western blot.Results:Compared with model group,the expressions of ROS,Aβ1-42 were down-regulated and the Nuclear Nrf2 and Whole-cell HO-1 were up-regulated in 20E2+PLE group.Conclusion:PLE can reduce the level of oxidative stress of model group effectively,it possibly reduce the aggregation of Aβ1-42 and prevent oxidizing via activating Nrf2/HO-1 pathway.