血管紧张素Ⅱ受体阻断剂对大鼠机械通气所致肺损伤的保护作用  

The protective role of angiotensinⅡreceptor inhibitor in ventilator-induced lung injury in rats

作　　者：冯丹[1] 姚尚龙[1] 尚游[1] 武庆平[1] 王立奎[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院麻醉科,武汉430022

出　　处：《中华急诊医学杂志》2007年第9期940-944,共5页Chinese Journal of Emergency Medicine

基　　金：国家自然科学基金(30571787);湖北省科技攻关计划(2005AA301C23)

摘　　要：目的研究血管紧张素Ⅱ受体阻断剂洛沙坦对大鼠机械通气所致肺损伤(VILI)的保护作用及其机制。方法40只健康SD大鼠随机均分成A、B、C、D四组:A组为对照组;B组为正常潮气量机械通气组,潮气量(V_T)为10 ml/kg;C组为大潮气量机械通气通气组,V_T为40 ml/kg;D组为大潮气量通气加洛沙坦处理组,V_T为40 ml/kg,D组大鼠实验前30 min用血管紧张素Ⅱ受体(AT1型)特异性阻断剂洛沙坦(Losartan)溶液30 mg/kg腹腔注射。B、C、D三组机械通气频率(P)均为80次/min,通气时间均为2 h。实验完毕收集肺组织和肺泡灌洗液标本。光镜观察肺病理改变,逆转录聚合酶链式反应(RT-PCR)法检测A、B、C三组肺组织中血管紧张素原的表达水平,TUNEL法检测肺组织细胞凋亡情况,同时测定肺灌洗液总蛋白、白细胞计数、肺湿/干比以及肺组织髓过氧化物酶(MPO)的水平。结果B组和A组各项指标差异无统计学意义;与A、B组相比,C组肺病理改变明显,肺细胞凋亡显著性增多,血管紧张素原的表达水平显著增高(P<0.01),肺湿/干比、总蛋白、白细胞计数、MPO等指标均显著性增高(P<0.01);与C组比较,D组肺病理改变明显减轻,肺细胞凋亡、肺湿/干比、总蛋白、白细胞计数、MPO等指标均显著性降低(P<0.05或P<0.01)。结论血管紧张素Ⅱ可能在VILI的致病机理中起着一定的作用,特异性阻断血管紧张素Ⅱ受体(AT1型)能显著减轻VILI时肺损伤和炎症反应的程度。Objective To study the protective role of Angiotensin Ⅱ receptor inhibitor in ventilator-induced lung injury of rats. Method Forty healthy male SD rats were equally divided into four group （A, B, C, D group, n = 10）. Group A served as control group, group B had low tidal volume （VT= 10 ml/kg） with breathing rate （P） = 80/min; group C had high tidal volume （VT = 40 ml/kg） group with breathing rate 80/min; group D had high tidal volume （VT = 40 ml/kg） group with breathing rate 80/min, all rats in group D were pretreated with Losartan. The duration of ventilation in all groups was two hours. Rats were sacrificed after experiment finished. The lung lavage liquid and lung tissue were collected and preserved with well established methods. Lung pathological change was observed by microscope; lung cell apeptosis was assessed with TUNEL; the expression of ANGⅡ was assayed with RT-PCR. The measured variables also included total protein, WBC, W/D, MPO. Results In comparison with B group, all variables in group C were significantly increased （ P 〈 0.01 ）. Whereas in comparison with group C, all variables measured in group D remarkably decreased （ P 〈 0.05 or 0.01. Conclusions ANG Ⅱ probably plays an important role in VILI, and the specific blocking agent of ANG Ⅱ receptor （AT1） can remarkably alleviate ventilator-induced lung injury.

关 键 词：机械通气所致肺损伤 机械通气 洛沙坦 

分 类 号：R96[医药卫生—药理学] R459.7[医药卫生—药学] R563