Abstract
Mechanical ventilation is an effective treatment for acute respiratory distress syndrome (ARDS), which can improve the prognosis of ARDS to a certain extent. However, it may further aggravate lung tissue injury, which is defined as ventilator-induced lung injury (VILI). Intermedin (IMD) belongs to the calcitonin gene-related peptide (CPRP) superfamily. Our previous studies have found that IMD reduces the expression proinflammatory cytokines, down-regulates nuclear translocation and improves the integrity of endothelial barrier in ARDS. However, the effect of IMD on VILI has not been clarified. Oxidative stress imbalance and apoptosis are the main pathophysiological characteristics of VILI. In the current study, we used C57B6/J mice and human pulmonary microvascular endothelial cells (HPMECs) to establish a VILI model to analyze the effects of IMD on VILI and explore its potential mechanism. We found that IMD alleviated lung injury and inflammatory response in VILI, mainly in reducing ROS levels, upregulating SOD content, downregulating MDA content, reducing the expression of Bax and caspase-3, and increasing the expression of Bcl-2. In addition, we also found that IMD played its anti-oxidative stress and anti-apoptotic effects via JAK2/STAT3 signaling. Our study may provide some help for the prevention and treatment of VILI.
Highlights
Acute respiratory distress syndrome (ARDS) is one of the most common critical diseases of the respiratory system, with high mortality and a heavy social burden (Matthay et al, 2019)
We used C57B6/J mice and human pulmonary microvascular endothelial cells (HPMECs) to establish a ventilator-induced lung injury (VILI) model to analyze the effect of IMD on VILI and its potential mechanism
We used IMD and IMD inhibitor to comprehensively confirm our hypothesis - IMD protected against VILI by alleviating oxidative stress and apoptosis
Summary
Acute respiratory distress syndrome (ARDS) is one of the most common critical diseases of the respiratory system, with high mortality and a heavy social burden (Matthay et al, 2019). Mechanical ventilation may aggravate lung tissue injury, mainly manifested in infiltration of neutrophils, formation of hyaline membrane, increase of apoptosis, up-regulation of vascular endothelial permeability and formation of pulmonary edema, which is called ventilator-related lung injury (Curley et al, 2016). Endothelial cells (ECs) are the earliest effector cells in lung injury (Matthay et al, 2019). Reducing endothelial cell injury and maintaining endothelial cell function is the key to alleviating endothelial permeability, reducing pulmonary edema, and reducing mortality (Qi et al, 2016; Huang et al, 2017). IMD is a homeostasis regulating peptide involved in many life activities, such as glucose and lipid metabolism, inhibition of inflammation, maintaining
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