ABSTRACT
The objective of the present study was to investigate the role of γ-aminobutyric acid type A receptor (GABA(A)R) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats. Thirty-two male wistar rats were randomly divided into four groups. Rats in the GABA group were pretreated with LPS and GABA, while those in the bicuculline (BIC) group were pretreated with LPS and bicuculline. We assessed the arterial blood gas, dry/wet ratio, and the level of tumor necrosis factor-α (TNF-α), IL-6, malondialdehyde, and superoxide dismutase 6 h after the immunization. Paraffin sections of samples were detected using the steptavidin-peroxidase method. Protein expression was detected using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blotting. PaO2 in the LPS group was significantly lower than that in the control rats. Activation of GABA-mediated signaling by GABA increased the expression of GABA(A)R in airway bronchial and alveolar epithelial cells. Blockade of the GABA(A)R by bicuculline limited the expression of this receptor. The GABA group rats had higher levels of tissue TNF-α and IL-6 than in ALI rats and control rats. The BIC group rats demonstrated an opposite expression level compared to the GABA group rats. Our results suggest that the GABA(A)R could aggravate the inflammatory response syndrome and oxidative stress in the lungs and play an essential role in LPS-induced acute lung injury. It provides a novel method to study the incidence and mortality of ALI during the peroperative period.