Study on the protective effect and mechanism of apelin-13 in ventilator-induced acute lung injury

Abstract

Abstract Background: Mechanical Ventilationventilation (MV) is an essential life support mechanism in the clinic. It may also lead to ventilator-induced acute lung injury (VILI) due to local alveolar overstretching and/or repeated alveolar collapse. However, the pathogenesis of VILI is not completely clear, and its occurrence and development may be related to inflammatory reactions, oxidative stress, apoptosis and other physiological processes. Some studies have found that the apelin/APJ pathway is an endogenous antagonistic mechanism that is activated during Acute respiratory distress syndrome(ARDS), and it can counteract the injury response and prevent uncontrolled lung injury. To prove that apelin-13 plays a protective role in VILI, in this study, we established a rat VILI model to explore whether apelin-13 can attenuate VILI in rats by inhibiting inflammation, cell apoptosis and oxidative stress. Methods: SD rats were divided into four groups: the control group, high tidal volume group, high tidal volume+NS group, and high tidal volume+apelin-13 group. After tracheotomy, autonomous breathing was maintained in the rats. After tracheotomy, the other rats were connected to a small animal ventilator for 4 hours to establish the rat VILI model. The mRNA expression of apelin was measured by real-time quantitative polymerase chain reaction (qRT‒PCR), and the protein expression levels of APJ, the apoptotic protein Bax, Bcl-2 and Akt/P-Akt were measured by Western blotting (WB) and immunofluorescence. The degree of lung injury was evaluated by pathological staining of lung tissue and measuring the wet to dry ratio of lung tissue. The expression of inflammatory factors in alveolar lavage fluid was measured by enzyme-linked immunosorbent assay (ELISA), and the activity of myeloperoxidase (MPO) in lung tissue was measured to evaluate the degree of pulmonary inflammation. Results: The expression of apelin and the APJ receptor was upregulated under VILI conditions. After the rats were treated with apelin-13, the activation of the apelin-APJ signaling pathway, the pathological damage to lung tissues, the degree of cell apoptosis, and the levels of the inflammatory cytokines IL-1, IL-6 and TNF-α were reduced in the VILI model rats. The expression of MPO was decreased, and the activity of MPO was also decreased. Moreover, the Akt/P-Akt signaling pathway is associated with apoptosis. After treatment, the expression of Akt/P-Akt pathway-related proteins increased. Conclusion: During VILI, the apelin/APJ axis plays an endogenous role in ameliorating injury. Overexpression of apelin can significantly reduce the inflammatory response, cell apoptosis and oxidative stress in the lung tissues of VILI model rats and slow the occurrence and development of VILI.