Suzhen Ji1, Leilei Wang2. 1. Department of Emergency, Cangzhou Central Hospital, Xinhua West Road, Cangzhou, 061000, Hebei, China. 2. Department of Neurosurgery, Cangzhou Central Hospital, Xinhua West Road, Cangzhou, 061000, Hebei, China.
Abstract
NEW FINDINGS: What is the central question of this study? The aim was to investigate the role of μ-opioid receptors in acute respiratory distress syndrome and whether their protective effect is mediated via the PI3K/Akt signalling pathway. What is the main finding and its importance? Our findings show that activation of μ-opioid receptors ameliorates lung injury, and the effects are reversed by the PI3K inhibitor, wortmannin. ABSTRACT: The main pathology of acute respiratory distress syndrome (ARDS) is the accumulation of inflammatory cells in the lung and increased permeability of vascular endothelial cells. The μ-opioid receptor (MOR) is a G-protein-coupled receptor, which stimulates angiogenesis and vascular endothelial cell proliferation. In addition, the MOR inhibits cell apoptosis via the PI3K/Akt signalling pathway. In this study, we aimed to explore the contribution of the MOR in ARDS and whether its effects are mediated via PI3K/Akt signalling. An ARDS model was established by intratracheal instillation of 5 mg kg-1 lipopolysaccharide (LPS). Lung injury was confirmed by Haematoxylin and Eosin staining, lung wet/dry weight ratio, bronchoalveolar lavage fluid protein concentrations, myeloperoxidase activity and vascular cell adhesion molecule 1 expression. Lung inflammation was determined by assessment of interleukin-1β and tumour necrosis factor-α concentrations. The protein level of p-Akt was detected by western blot. Endomorphin-1-activated MORs attenuated LPS-induced lung injury, lung wet/dry weight ratio, bronchoalveolar lavage fluid protein concentrations, myeloperoxidase activity, interleukin-1β and tumour necrosis factor-α levels and vascular cell adhesion molecule 1 expression, and elevated LPS-induced decreased p-Akt expression. However, the protective effect of MOR activation on lung injury was reversed by the PI3K inhibitor, wortmannin. In conclusion, MOR involvement in LPS-induced ARDS is via the PI3K/Akt pathway.
NEW FINDINGS: What is the central question of this study? The aim was to investigate the role of μ-opioid receptors in acute respiratory distress syndrome and whether their protective effect is mediated via the PI3K/Akt signalling pathway. What is the main finding and its importance? Our findings show that activation of μ-opioid receptors ameliorates lung injury, and the effects are reversed by the PI3K inhibitor, wortmannin. ABSTRACT: The main pathology of acute respiratory distress syndrome (ARDS) is the accumulation of inflammatory cells in the lung and increased permeability of vascular endothelial cells. The μ-opioid receptor (MOR) is a G-protein-coupled receptor, which stimulates angiogenesis and vascular endothelial cell proliferation. In addition, the MOR inhibits cell apoptosis via the PI3K/Akt signalling pathway. In this study, we aimed to explore the contribution of the MOR in ARDS and whether its effects are mediated via PI3K/Akt signalling. An ARDS model was established by intratracheal instillation of 5 mg kg-1 lipopolysaccharide (LPS). Lung injury was confirmed by Haematoxylin and Eosin staining, lung wet/dry weight ratio, bronchoalveolar lavage fluid protein concentrations, myeloperoxidase activity and vascular cell adhesion molecule 1 expression. Lung inflammation was determined by assessment of interleukin-1β and tumour necrosis factor-α concentrations. The protein level of p-Akt was detected by western blot. Endomorphin-1-activated MORs attenuated LPS-induced lung injury, lung wet/dry weight ratio, bronchoalveolar lavage fluid protein concentrations, myeloperoxidase activity, interleukin-1β and tumour necrosis factor-α levels and vascular cell adhesion molecule 1 expression, and elevated LPS-induced decreased p-Akt expression. However, the protective effect of MOR activation on lung injury was reversed by the PI3K inhibitor, wortmannin. In conclusion, MOR involvement in LPS-induced ARDS is via the PI3K/Akt pathway.