Inhibition of multidrug resistance-associated protein 4 protects against pulmonary vascular endothelial barrier dysfunction in septic rats / 中华急诊医学杂志

ABSTRACT

Objective To explore the effects of multidrug resistance-associated protein 4 (MRP4) inhibition on pulmonary vascular endothelial barrier dysfunction in septic rats.Methods Sixty Sprague Dawley rats were randomly (random number) divided into three groups:sham-operated group,sepsis group,and sepsis plus MRP4 inhibitor treatment group,with 20 rats in each group.Sepsis was induced by cecal ligation and puncture.MRP4 inhibitor MK571 (20 mg/kg) was administrated by intraperitoneal injection 30 minutes before induction of sepsis.Twenty-four later,serum interlukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels were measured by enzyme-linked immunosorbent assay.Lung injury was assessed by histopathological examination.Lung vascular permeability was evaluated by quantitation of Evans blue dye extravasation from vascular space to lung parenchyma.Results Compared with sham group,serum IL-6 and TNF-α levels were significantly higher in sepsis group.In addition,lung injury and lung vascular permeability were elevated in sepsis group compared to sham group.Importantly,MRP4 inhibitor treatment significantly decreased serum IL-6 and TNF-α levels,improved lung injury and reduced lung vascular permeability in septic rats.Conclusions Inhibition of MRP4 protects against pulmonary vascular endothelial barrier dysfunction in septic rats.