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目的探讨中性粒细胞肺内集聚在急性呼吸窘迫综合征(ARDS)发病机制中的作用。方法将健康成年雄性SD大鼠随机分为对照组和ARDS模型组,经股静脉注射油酸(0.12 ml/kg)制作ARDS模型,对照组经股静脉注射等量生理盐水。而后,在不同时间点插管至颈动脉采集颈动脉血做血气分析,经肺动脉圆锥插管至肺动脉采血测血常规,采用ELISA方法对肺组织匀浆进行髓过氧化物酶(MPO)定量检测及肺组织病理学检查和评分,并检测肺组织自由基的电子自旋共振(ESR)波谱。结果模型组大鼠动脉氧分压在染毒后10 min时就开始下降,氧合指数具有相同的变化规律,2 h后达到其最低值(为189.45 mm Hg),达到了ARDS的诊断标准(<200 mm Hg)。与对照组比较,模型组肺动脉全血白细胞总数和中性粒细胞数在注射后1 h开始下降,最低值分别出现在染毒后3 h和1～3 h,平均值为4.46×109/L和1.82×109/L～2.16×109/L,6 h后,白细胞总数和中性粒细胞计数升高(平均值分别达到11.68×109/L和5.93×109/L);此外,模型组给予油酸后2 h,中性粒细胞百分比即见升高,6 h左右达到最高峰(平均值为58.25%),以后逐渐下降,而对照组肺动脉血和外周动脉血的白细胞分类均以淋巴细胞为主。模型组肺组织中的活性氧(ROS)含量在注射后10 min已见升高,1 h达到峰值(约为正常水平的6.5倍),峰值出现早于血氧下降。模型组肺组织的MPO活力在注射油酸后30 min见明显升高,2 h左右达到最大值(平均值为5.82 U/g),约6 h后逐渐降低,但24 h时与对照组比较仍有统计学意义。肺组织改变在注射油酸后10 min(病理评分平均值为4.33)已经出现;30 min(病理评分平均值为6.51)其变化与对照组比较有统计学意义;6 h时(病理评分平均值为9.78)已十分严重。结论肺内失控的炎症损伤是ARDS病程的核心环节,而肺内大量中性粒细胞集聚及其产生的大量ROS则可能是其最重要的启动因子,也是ARDS损伤启动的重要信号。
Objective To investigate the role of neutrophil accumulation in the pathogenesis of acute respiratory distress syndrome (ARDS). Methods Healthy adult male Sprague-Dawley rats were randomly divided into control group and ARDS model group. ARDS model was established by intracerebral injection of oleic acid (0.12 ml / kg), and control group received normal saline through femoral vein. Then, at different time points intubated to the carotid artery to collect carotid blood for blood gas analysis, pulmonary conization to the pulmonary artery blood sampling and blood routine, ELISA method for lung tissue homogenate myeloperoxidase (MPO) quantitative detection And lung histopathological examination and scoring, and detected the electron spin resonance (ESR) spectrum of free radicals in lung tissue. Results The arterial oxygen pressure of model rats began to decline 10 min after exposure, and the oxygenation index had the same change rule. After 2 h, the oxygen partial pressure reached its lowest value (189.45 mm Hg) and reached the diagnostic criteria of ARDS <200 mm Hg). Compared with the control group, the total number of leukocytes and neutrophils in the whole pulmonary artery began to decrease at 1 h after injection, with the lowest values occurring at 3 h and 1 h to 3 h after exposure, respectively, with an average value of 4.46 × 109 / L And 1.82 × 109 / L ~ 2.16 × 109 / L respectively. After 6 hours, the total number of leukocytes and neutrophil count increased (the average values reached 11.68 × 109 / L and 5.93 × 109 / L, respectively). In addition, After 2 h of oleic acid, the percentage of neutrophils increased, reached its peak at 6 h (average value was 58.25%), and then decreased gradually. In the control group, the leukocyte classification of pulmonary artery and peripheral arterial blood were expressed in lymphocytes Mainly. The level of reactive oxygen species (ROS) in the lung tissue of the model group increased at 10 min after injection, peaked at 1 h (about 6.5 times of the normal level), and peaked earlier than that of the blood oxygen. In the model group, the MPO activity in the lung tissue increased significantly at 30 min after injection of oleic acid and reached the maximum at about 2 h (mean, 5.82 U / g), and gradually decreased after about 6 h, but at 24 h, compared with the control group Still statistically significant. The changes of lung tissue ten minutes after the injection of oleic acid (pathological score average of 4.33) have been; 30 min (pathological score of 6.51) the changes were statistically significant compared with the control group; 6 h (pathological score average 9.78) has been very serious. Conclusion The uncontrolled inflammatory injury in the lungs is the core of the ARDS process. The accumulation of large numbers of neutrophils in the lungs and the large amount of ROS produced in the lungs may be the most important initiating factor and an important signal for the initiation of ARDS injury.