内皮型一氧化氮合酶在机械通气相关性肺损伤小鼠炎性反应中的作用：基因敲除法  

Role of endothelial nitric oxide synthase in inflammatory response in mice with ventilator-induced lung injury ： gene knockout

作　　者：钟琦[1] 陈畅[1] 张宗泽[1] 彭勉[1] 陈凯[1] 陈莹莹[1] 王焱林[1] 

机构地区：[1]武汉大学中南医院麻醉科,430071

出　　处：《中华麻醉学杂志》2015年第1期40-43,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（81000318）;湖北省自然科学基金（2012FFA093）;武汉青年科技晨光计划项目（201271031425）

摘　　要：目的 采用基因敲除法评价肉皮型一氧化氮合酶（eNOS）在机械通气相关性肺损伤小鼠炎性反应中的作用.方法 SPF级雄性C578L/6J小鼠（野生）和B6.129P2-Nos3tm1Unc/NJU小鼠（eNOS基因敲除）各24只,10～12周龄,体重20～ 25 g,采用随机数字表法,将2种小鼠各分为2组（n=12）：假手术组（S组）和机械通气组（MV组）.机械通气相关性肺损伤模型的制备：气管插管后,机械通气,吸入氧浓度50％,氧流量0.5 L/min,通气频率70次/min,潮气量15 ml/kg,PEEP 2cmH2O.机械通气4h时,采集颈内动脉血样,测定PaO2,随后取肺组织,测定湿重/干重（W/D）比值、髓过氧化物酶（MPO）活性、丙二醛（MDA）、IL-6、肿瘤坏死因子-α（TNF-α）、NO的含量和肺微血管通透性;电镜下观察肺组织病理学结果.结果 与野生小鼠的S组比较,野生小鼠和eNOS基因敲除小鼠的MV组PaO2降低,肺组织W/D比值、MPO活性、MDA、IL-6、TNF-α、NO的含量和肺微血管通透性升高（P＜0.05）,eNOS基因敲除小鼠的S组上述指标差异无统计学意义（P＞0.05）;与野生小鼠的MV组比较,eNOS基因敲除小鼠的MV组PaO2升高,肺组织W/D比值、MPO活性、MDA、IL-6、TNF-α、NO的含量和肺微血管通透性降低（P＜0.05）.eNOS基因敲除小鼠的MV组肺组织病理学损伤明显轻于野生小鼠的MV组.结论 eNOS参与了机械通气相关性肺损伤小鼠炎性反应.Objective To evaluate the role of endothelial nitric oxide synthase （eNOS） in inflammatory responses in mice with ventilator-induced lung injury using gene knockout.Methods Twenty-four male C578L/6J wild type mice and 24 male B6.129P2-Nos3tm1Unc/NJU （eNOS gene knockout） mice,aged 10-12 months,weighing 20-25 g,were randomly assigned into 2 groups （n=12 each） using a random number table：sham operation group （group S） and mechanical ventilation group （group MV）.The animals were anesthetized with intraperitoneal 1% pentobarbital sodium 70 mg/kg,and mechanically ventilated after tracheal intubation.The animals were mechanically ventilated for 4 h （oxygen flow rate 0.5 L/min,FiO2 50%,VT 15 ml/kg,RR 70 bpm,PEEP 2 cmH2O）.After 4 h of ventilation,blood samples were obtained from the internal carotid artery for detection of PaO2.The animals were then sacrificed and the lungs were removed for determination of wet/dry lung weight （W/D） ratio,myeloperoxidase （MPO） activity,contents of malondialdehyde （MDA）,interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）,and pulmonary microvascular permeability,and for microscopic examination of the pathological changes of lung （with electron microscope）.Results Compared with group S of wild type mice,PaO2 was significantly decreased,while W/D ratio,MPO activity,contents of MDA,IL-6,TNF-oα and NO,and pulmonary microvascular permeability were increased in MV groups of wild type and gene knockout mice,and no significant change was found in the parameters mentioned above in group S of gene knockout mice.Compared with group MV of wild type mice,PaO2 was significantly increased,while W/D ratio,MPO activity,contents of MDA,IL-6,TNF-α and NO and pulmonary microvascular permeability were decreased in group MV of gene knockout mice.The pathological changes of lung were significantly attenuated in group MV of gene knockout mice as compared with group MV of wild type mice.Conclusion eNOS is involved in inflammatory responses in mice with vent

关 键 词：一氧化氮合酶Ⅲ型 呼吸 人工 呼吸窘迫综合征 成人 炎症 

分 类 号：R563[医药卫生—呼吸系统]