洛沙坦对糖尿病小鼠机械通气相关肺损伤的影响  

Effect of losartan on mechanical ventilation-induced lung injury in diabetic mice CHEN Chang

作　　者：陈畅[1] 李子嘉[2] 李涓[3] 彭勉[1] 陈莹莹[1] 王焱林[1] 张宗泽[1] 

机构地区：[1]武汉大学中南医院麻醉科,430071 [2]中山大学附属第六医院麻醉科 [3]中南大学湘雅医院麻醉科

出　　处：《中华麻醉学杂志》2012年第10期1235-1238,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（81000318）;武汉青年科技晨光计划项目（201271031425）;武汉大学青年教师资助项目（4101003）

摘　　要：目的评价洛沙坦对糖尿病小鼠机械通气相关肺损伤的影响。方法SPF级雌性C57／BL6小鼠48只，10—12周龄，体重20～25g，采用随机数字表法，将小鼠随机分为3组（n=16）：对照组（c组）、糖尿病机械通气组（DM组）和洛沙坦组（L组）。DM组和L组采用腹腔注射链脲佐菌素150mg／kg的方法制备糖尿病模型。取糖尿病模型制备成功的小鼠进行机械通气4h，吸入氧浓度50％，通气频率70次／min，潮气量15ml／kg，PEEP2cm H2O2 L组于机械通气前30min腹腔注射洛沙坦30mg／kg。机械通气4h时采集颈动脉血样，测定PaO2，随后处死，取肺组织，测定湿／干重比（W／D比）、髓过氧化物酶（MPO）活性和肺微血管通透性；采用实时荧光定量RT-PCR法测定血管紧张素Ⅱ（AngⅡ）受体ATlmRNA的表达水平；ELISA法测定AngⅡ的含量；Westernblot法测定细胞核内NF．KBp65的表达水平。结果与C组比较，DM组和L组PaO2降低，肺组织W／D比、MPO活性、肺微血管通透性和AngIi含量升高，ATlmRNA和NF．KBp65表达上调（P〈0．05）；与DM组比较，L组PaO2升高，肺组织W／D比、MPO活性、肺微血管通透性和Angll含量降低，ATlmRNA和NF—xBp65表达下调（P〈0．05）。结论洛沙坦通过抑制ATl受体和AngⅡ水平，从而改善肺微血管通透性和抑制NF-xB活化，减轻糖尿病小鼠机械通气相关肺损伤。Objective To evaluate the effect of losartan on mechanical ventilation-induced lung injury in diabetic mice. Methods Forty-eight female SPF C57/BL6 mice, aged 10-12 months, weighing 20-25 g, were randomly assigned into 3 groups （n = 16 each）： control group （group C）, diabetes ＋ mechanical ventilation （group DM） and losartan group （group L）. Diabetes mellitus was induced by intraperitoneal streptozotocin 150 mg/kg and confirmed by blood glucose level 〉 16 mmol/L in groups DM and L. Diabetic mice were mechanically ventilated （FiO250%, VT 15 ml/kg, RR 70 bpm, PEEP 2 cm H2O） for 4 h. Losartan 30 mg/kg was injected intraperitoneally 30 min before ventilation in group L,. Eight mice from each group were chosen at 4 of ventilation and arterial blood samples were obtained for detection of PaO2 The animals were then sacrificed and the lungs were removed for determination of W/D lung weight ratio, myeloperoxidase （MPO） activity, pulmonary microvascular permeability, angiotensin Ⅱ （ Ang Ⅱ ） receptor AT1 mRNA expression （ by RT-PCR）, Ang Ⅱ content and nuclear factor kappa B （NF-kB） p65 expression （by Western blot）. Results Compared with group C, PaO2 was significantly decreased, while W/D lung weight ratio, MPO activity, pulmonary microvascular permeability andAng Ⅱ content were significantly ＇increased, and the expression of AT1 mRNA and NF-kB p65 was upregulated in groups DM and L （P 〈 0.05）. PaO2 was significantly higher, and W/D lung weight ratio, MPO activity, pulmonary microvascular permeability, Ang Ⅱ content and the expression of AT1 mRNA and NF-kB p65 were significantly lower in group L than in group DM （ P 〈 0.05 ）. Conchmion Losartan can reduce mechanical ventilation-induced lung injury in diabetic mice through inhibiting AT1 receptor and Ang II levels and improving pulmonary microvascular permeability and inhibiting NF-kB activation.

关 键 词：洛沙坦 糖尿病 呼吸 人工 呼吸窘迫综合征 成人 

分 类 号：R285.5[医药卫生—中药学]