Inflammation response and oxidative stress play important roles in
acute lung injury (ALI). Activation of the
cAMP/protein kinase A (PKA) signaling pathway may attenuate ALI by suppressing immune responses and inhibiting the generation of
reactive oxygen species (ROS).
Hydroxysafflor yellow A (HSYA) is a natural
flavonoid compound that reduces oxidative stress and inflammatory
cytokine-mediated damage. In this study, we examined whether HSYA could protect the lungs from
oleic acid (OA)-induced injury, which was used to mimic ALI, and determined the role of the cAMP/PKA signaling pathway in this process. Arterial
oxygen tension (PaO2),
carbon dioxide tension, pH, and the PaO2/fraction of inspired
oxygen ratio in the blood were detected using a blood gas analyzer. We measured wet/dry lung weight ratio and evaluated tissue morphology. The
protein and inflammatory
cytokine levels in the bronchoalveolar lavage fluid and serum were determined using
enzyme-linked immunoassay. The activities of
superoxide dismutase,
glutathione peroxidase, PKA, and
nicotinamide adenine dinucleotide phosphate oxidase, and the concentrations of cAMP and
malondialdehyde in the lung tissue were detected using assay kits. Bcl-2, Bax,
caspase 3, and p22(
phox) levels in the lung tissue were analyzed using Western blotting. OA increased the inflammatory
cytokine and ROS levels and caused lung dysfunction by decreasing cAMP synthesis, inhibiting PKA activity, stimulating
caspase 3, and reducing the Bcl-2/Bax ratio.
H-89 increased these effects. HSYA significantly increased the activities of
antioxidant enzymes, inhibited the inflammatory response via cAMP/PKA pathway activation, and attenuated OA-induced
lung injury. Our results show that the cAMP/PKA signaling pathway is required for the protective effect of HSYA against ALI.