Abstract
Lung ischemia–reperfusion injury is a common clinical concern. As the injury occurs, the pulmonary afferent nerves play a key role in regulating respiratory functions under pathophysiological conditions. The present study was to examine products of oxidative stress and expression of transient receptor potential A1 in the commissural nucleus of the solitary tract after lung ischemia–reperfusion injury; and further to determine molecular mediators linking to activation of oxidative stress and transient receptor potential ankyrin A1. A rat model of lung ischemia–reperfusion injury was used. Enzyme-linked immunosorbent assay and western blot analysis were employed to examine products of oxidative stress (i.e. 8-isoprostaglandin F2α and 8-hydroxy-2′-deoxyguanosine), and expression of transient receptor potential A1, Nrf2-antioxidant response element, and NADPH oxidase. 8-isoprostaglandin F2α and 8-hydroxy-2′-deoxyguanosine were amplified in the commissural nucleus of the solitary tract of lung ischemia–reperfusion injury rats, accompanied with downregulation of Nrf2-antioxidant response element, and upregulation of NOX4 and transient receptor potential A1. Blocking NADPH oxidase (subtype NOX4) decreased products of oxidative stress in the commissural nucleus of the solitary tract and attenuated upregulation of transient receptor potential A1 induced by lung ischemia–reperfusion injury. Our data revealed specific signaling pathways by which lung ischemia–reperfusion injury impairs Nrf2-antioxidant response and activates oxidative stress in the brainstem thereby leading to amplification of transient receptor potential A1 receptor likely via products of oxidative stress. Data suggest the abnormalities in the pulmonary afferent signals at the brainstem level which is likely to affect respiratory functions as lung ischemia–reperfusion injury occurs.