γ-aminobutyric acid alleviates LPS-induced acute lung injury in mice through upregulating type B receptors.

Abstract

In recent years, studies have shown that GABA has a certain therapeutic effect on acute lung injury (ALI), but its specific mechanism has not been fully elucidated. The study was designed to investigate the protective effect and mechanism of γ-aminobutyric acid (GABA) on ALI induced by lipopolysaccharide (LPS) in mice. C57BL/6 mice were randomly divided into a control group, LPS group, LPS + GABA (10 mg/kg) group and LPS + dexamethasone (Dex, 5 mg/kg) group. The survival rate of each group was observed at different time points after modeling. The levels of tumor necrosis factor α (TNF-α), interleukin (IL) 1β, 10, myeloperoxidase (MPO) and the cell count and protein concentration in bronchoalveolar lavage fluid (BALF) were measured. Lung histopathology and the expression of GABA receptors were observed by HE staining and immunohistochemistry respectively. Lung water content was assessed by wet-dry weight ratio. GABA could significantly improve the survival rate and prolong the survival time of animals, alleviate the degree of inflammatory injury and pulmonary edema, reduce the content of MPO, down-regulate the levels of pro-inflammatory cytokines IL-1β and TNF-α, and up-regulate the expression of anti-inflammatory cytokine IL-10. Moreover, GABA could significantly decrease the expression of type A receptors and enhance type B receptors. GABA can effectively alleviate ALI induced by LPS in mice, and its effect may be related to the upregulation of type B receptors.