摘要目的 探讨抑制多药耐药相关蛋白4 (MRP4)对脓毒症大鼠肺血管内皮屏障功能的影响.方法 60只Sprague Dawley大鼠随机(随机数字法)分为假手术组、脓毒症组和MRP4抑制剂干预组,每组20只动物.脓毒症模型采用盲肠结扎穿孔法.MRP4抑制剂干预组于脓毒症模型建立前30 min腹腔注射MRP4抑制剂MK571 (20 mg/kg).术后24h,采用ELISA法检测血清促炎细胞因子白介素-6 (IL-6)和肿瘤坏死因子-α(TNF-α)水平,取肺组织做病理学检查,用伊文思蓝法测定肺组织渗透性.结果 与假手术组大鼠相比,脓毒症组大鼠血清IL-6和TNF-α水平显著升高,肺组织损伤明显,肺组织渗透性增强.与脓毒症大鼠组比较,MRP4抑制剂干预组大鼠血清IL-6和TNF-α水平明显降低,肺组织病理损伤减轻,肺组织渗透性减弱.结论 抑制MRP4可显著改善脓毒症大鼠肺血管内皮屏障功能障碍.

abstractsObjective 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.