Effect of amiloride pretreatment on lipopolysaccharide-induced acute lung injury in rats

Abstract

Objective To investigate the effect of amiloride pretreatment on the acute lung injury (ALI)induced by lipopolysaccharide (LPS) in rats. Methods Thirty-two pathogen-free male SD rats weighing 200-250 g were randomly divided into 4 groups (n = 8 each); group Ⅰ received iv normal saline (group C); group Ⅱ ALI received iv LPS 6 mg/kg (group ALI); group Ⅲ received iv amiloride 10 mg/kg (group A) and group Ⅳ received amiloride 10 mg/kg iv 30 min before iv LPS ( group AL). The animals were killed by exsanguination at 6 h after iv LPS infusion. The lungs were immediately removed. Microscopic examination of lung tissue was performed. The left lung was lavaged. The total protein (TP), TNF-α and macrophage inflammatory protein-2 (MIP-2)concentrations in broncho-alveolar lavage fluid (BALF) were measured. The W/D weight ratio and the myeloperoxidase (MPO) activity and expression of Na-H exchanger-1 ( NHE1 ), p38MAPK and extracellular signal-regulated kinase (ERK) in lung tissue were determined. Results LPS significantly increased ALI score (0 = slightest, 4 = severest), W/D lung weight ratio, TP, TNF-α and MIP-2 concentrations in BALF and MPO activity and the expression of NHE1, p38MAPK and ERK in the lung as compared with. control group. Amiloride pretreatment significantly attenuated LPS-induced changes except p38MAPK expression. Conclusion Pretreatment with amiloride can attenuate LPS-induced ALI by inhibition of ERK activation. Key words: Amiloride; Respiratory distress syndrome, adult; Endotoxemia; Pretreatment