去铁胺对大鼠呼吸机相关性肺损伤的影响

Effect of deferoxamine on ventilator-associated lung injury in rats

目的评价去铁胺对大鼠呼吸机相关性肺损伤影响。方法健康雄性SD大鼠24只,体重250~300g,6~8周龄,采用随机数字表法分为3组(n=8):对照组(C组)、呼吸机相关性肺损伤组(VALI组)和呼吸机相关性肺损伤+去铁胺组(VALI+DFO组)。C组和VALI组腹腔注射生理盐水2ml,VALI+DFO组腹腔注射去铁胺200mg/kg(溶于2ml生理盐水中);15min后VALI组和VALI+DFO组连接小动物呼吸机行容量控制通气4h,潮气量40ml/kg,通气频率40~60次/min,呼吸比1∶1。机械通气结束后处死大鼠,取左肺组织,光镜下观察病理学结果,并行病理损伤评分,计算湿重/干重(W/D)比值;行右肺灌洗,收集灌洗液,制备巨噬细胞悬液,采用流式细胞术测定巨噬细胞和线粒体ROS水平。结果与C组比较,VALI组肺组织病理损伤评分和W/D比值升高,肺泡巨噬细胞及线粒体ROS水平升高,VALI+DFO组肺组织病理损伤评分升高(P<0.05)。与VALI组比较,VALI组+DFO组肺组织病理损伤评分和W/D比值降低,肺泡巨噬细胞及线粒体ROS水平降低(P<0.05)。结论去铁胺可减轻大鼠呼吸机相关性肺损伤,其机制可能与抑制氧化应激反应有关。

Objective To evaluate the effect of deferoxamine on ventilator-associated lung injury in rats. MethodsTwenty-four healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 250-300 g, were divided into 3 groups (n=8 each) using a random number table method: control group (group C), ventilator-associated lung injury group (group VALI), and ventilator-associated lung injury plus deferoxamine group (VALI+ DFO group). Normal saline 2 ml was intraperitoneally injected in C and VALI groups, and deferoxamine 200 mg/kg (dissolved in 2 ml normal saline) was intraperitoneally injected in group VALI+ DFO.The animals were connected to a small animal ventilator 15 min later and mechanically ventilated in volume-controlled mode, with tidal volume 40 ml/kg, respiratory rate 40-60 breaths/min, inspiratory/expiratory ratio 1∶1, and inspired oxygen fraction ratio 1.0.The rats were sacrificed after the end of mechanical ventilation, and the left lung tissues were removed for examination of the pathological changes (with a light microscope) which were scored and for determination of wet/dry weight ratio (W/D ratio). The right lung was lavaged, and lavage fluid was collected to prepare macrophage suspension, and the alveolar macrophage and mitochondrial reactive oxygen species (ROS) levels were determined using flow cytometry. Results Compared with group C, the pathological score, W/D ratio of lung tissues, and alveolar macrophage and mitochondrial ROS levels were significantly increased in group VALI, and the pathological score was significantly increased in group VALI (P<0.05). Compared with group VALI, the pathological score, W/D ratio of lung tissues, and alveolar macrophage and mitochondrial ROS levels were significantly decreased in group VALI and DFO (P<0.05). Conclusion Deferoxamine can reduce ventilator-associated lung injury, and the mechanism may be related to inhibiting oxidative stress in rats.