氯沙坦对急性肺损伤/急性呼吸窘迫综合征的治疗作用  

Losartan Alleviates Lung Inflammation of Rats with Acute Lung Injury

作　　者：沈利汉[1] 莫红缨[2] 蔡立华[1] 覃炳军[1] 肖正伦[2] 

机构地区：[1]东莞市人民医院ICU,广东东莞523018 [2]广州呼吸疾病研究所,广东广州510120

出　　处：《中国呼吸与危重监护杂志》2010年第4期409-412,共4页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：英东重症医学科研基金(编号:303001021)

摘　　要：目的研究肾素-血管紧张素系统(RAS)药物氯沙坦在急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)治疗中的作用。方法采用盲肠结扎穿孔术(CLP)复制小鼠ALI/ARDS模型,术后分别腹腔注射不同浓度氯沙坦(5、10、15、20、25mg/kg),研究氯沙坦对ALI/ARDS小鼠肺损伤的影响,并观察氯沙坦作用后ALI/ARDS小鼠7d生存率的变化。结果氯沙坦显著改善ALI/ARDS小鼠肺损伤的程度,在5～15mg/kg范围内,ALI/ARDS小鼠的氧合指数和肺湿重/干重比(W/D)显示改善的趋势;但当氯沙坦的浓度超过15mg/kg时,氧合指数和W/D反而逐渐变差。氯沙坦(15mg/kg)干预使小鼠血清中TNF-α[(554.1±62.7)pg/mL比(759.2±21.5)pg/mL,P<0.01]、IL-6[(1227.3±130.0)pg/mL比(2670.4±174.1)pg/mL,P<0.01]和IL-1β[(444.0±38.6)pg/mL比(486.6±61.7)pg/mL,P<0.05]水平均显著降低;肺水肿明显减轻;小鼠7d生存率显著提高(6.7%比0)。结论在一定剂量范围内RAS药物氯沙坦可减轻CLP诱导的ALI/ARDS肺损伤,提高ALI/ARDS小鼠7d生存率。Objective To investigate the role of angiotensin-II type 1 receptor （AT1） antagonist in treatment of acute lung injury/acute respiratory distress syndrome （ALI/ARDS）.Methods Animal model of ALI/ARDS was induced by cecal ligation and perforation （CLP）.ALI/ARDS animals received a separate intraperitoneal injection of several concentrations（5,10,15,20,25 mg/kg） of AT1 inhibitor losartan after CLP,then the changes of lung injury and 7-day survival were measured.Results Oxygenation index and lung wet to dry weight ratio （W/D） showed an improving trend when losartan was administered at doses of 5 to 15 mg/kg in ALI/ARDS rats,but aggravated above the dose of 15 mg/kg.Losartan （15 mg/kg） treatment significantly alleviated pulmonary edema after CLP operation,and decreased serum levels of TNF-α,IL-6,and IL-1β [TNF-α：（554.1±62.7）pg/mL vs.（759.2±21.5）pg/mL,P0.01;IL-6：（1227.3±130.0）pg/mL vs.（2670.4±174.1）pg/mL,P0.01;IL-1β：（444.0±38.6）pg/mL vs.（486.6±61.7）pg/mL,P0.05].7-day survival rate also increased in losartan treatment group at a dose of 15 mg/kg（6.7% vs.0）.Conclusions The AT1 inhibitor,losartan,can significantly prevent lung injury in ALI/ARDS after CLP,and improve the 7-day survival rate.

关 键 词：急性肺损伤/急性呼吸窘迫综合征 肾素-血管紧张素系统 血管紧张素Ⅱ受体1拮抗剂 氯沙坦 

分 类 号：R563.8[医药卫生—呼吸系统]