外源性保护素DX对脓毒症小鼠急性肺损伤的影响

Effect of exogenous protectin DX on acute lung injury in septic mice

目的探讨外源性保护素DX（PDX）对脓毒症小鼠急性肺损伤的影响。方法雄性C57BL／6小鼠30只，6～8周龄，体重20～25g，采用随机数字表法分为3组（n=10）：假手术组（Sham组）、脓毒症组（S组）和PDX组。采用盲肠结扎穿孔（CLP）法制备脓毒症模型。于CLP后1h时，PDX组腹腔注射PDX 300ng，Sham组和S组注射等容量生理盐水。于CLP后24h时处死小鼠，收集肺泡灌洗液（BALF），测定蛋白浓度和IL-1β、TNF—α、IL-6和IL-10浓度；取肺组织，观察病理学结果，进行肺损伤评分，测定髓过氧化物酶（MPO）活性、湿重／干重（W／D）比值和NF—κB p65磷酸化水平。结果与Sham组比较，S组和PDX组肺损伤评分、MPO活性、W／D比值、NF—κB p65磷酸化水平以及BALF蛋白浓度和炎性因子浓度升高（P〈0．05）；与S组比较，PDX组肺损伤评分、MPO活性、W／D比值、NF-κB p65磷酸化水平以及BALF蛋白浓度和IL-1β、TNF—α、IL-6浓度降低，IL-10浓度升高（P〈0．05）。结论外源性PDX可抑制肺组织NF—κB活性从而减轻脓毒症小鼠急性肺损伤。

Objective To investigate the effect of exogenous protectin DX （PDX） on acute lung injury in septic mice. Methods Thirty male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were randomly divided into 3 groups （n= 10 each） using a random number table： sham operation group （Sham group） , sepsis group （ S group） and PDX group. Sepsis was produced by cecum ligation and puncture （CLP） in the mice anesthetized with pentobarbital sodium. At 1 h after CLP, PDX 300 ng was injected intraperitoneally in PDX group, and the equal volume of normal saline was given in Sham and S groups. At 24 h after CLP, the mice were sacrificed, and the broncho-alveolar lavage fluid （BALF） was collected for determination of interleukin-lbeta （IL-1β） , tumor necrosis factor-alpha （TNF-α） , IL-6 and IL-10 concentrations, and the lungs were removed for microscopic examination and for determination of the myeloperoxidase （MPO） activity, wet/dry lung weight ratio （W/D ratio） and phosphorylation of nuclear factor-kappa B （NF-κB） p65. Lung injury scores were calculated. Results Compared with Sham group, the lung injury score, MPO activity, W/D ratio, phosphorylation of NF-κB p65, and concentrations of protein and inflammatory factors in BALF were significantly increased in S and PDX groups （P〈0.05）. Compared with S group, the lung injury score, MPO activity, W/D ratio, phosphorylation of NF-κB p65, and concentra- tions of protein, IL-1β, TNF-α and IL-6 in BALF were significantly decreased, and the concentration of IL-10 in BALF was significantly increased in PDX group （P〈0.05）. Conclusion Exogenous PDX can alleviate acute lung injury through inhibiting NF-κB activity in the lung tissues of septic mice.