Abstract
The aim of the present study was to investigate the effects of diammonium glycyrrhizinate lipid ligand (DGLL) treatment on acute lung injury (ALI) and pulmonary edema induced by lipopolysaccharide (LPS) in Sprague-Dawley rats. Rats orally received 30, 60 and 120 mg/kg DGLL. After 1 h, the rat ALI model was established by LPS (10 mg/kg) intraperitoneal injection. After 6 h, lung injury was evaluated using hematoxylin and eosin staining techniques. Pulmonary edema was evaluated using lung wet-dry weight ratio, protein concentrations in the bronchoalveolar lavage fluid (BALF) and Evans blue (EB) extravasation in lung tissue. The expression levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in lung tissues were measured using ELISA. Myeloperoxidase (MPO) expression levels were detected by immunohistochemical staining. Western blotting was used to measure the expression level changes of intercellular adhesion molecule (ICAM)-1, as well as adherent and tight junction proteins, including vascular endothelial (VE)-cadherin, zonula occludens (ZO)-1, occludin and junctional adhesion molecule (JAM)-1 that were associated with pulmonary inflammation and microvascular permeability. DGLL treatment significantly alleviated ALI induced by LPS, which was demonstrated by reduction of MPO-positive cells and expression levels of TNF-α, IL-1β and ICAM-1 in rat lung tissues. In addition, DGLL abrogated LPS-induced pulmonary edema, decreased the protein concentration in BALF and reduced EB extravasation. DGLL also reversed the reduced expression of VE-cadherin and tight junction proteins, including ZO-1, occludin and JAM-1 in the lung tissues caused by LPS. In conclusion, DGLL exhibits a protective effect on LPS-induced rat ALI, which is associated with the inhibition of inflammatory cell infiltration and microvascular barrier disruption. The present results provide a theoretical basis for the application of DGLL for the potential clinical treatment of ALI.