氯沙坦对大鼠内毒素性急性肺损伤的影响及可能机制

Protective effect and possible mechanism of losartan on endotoxin-induced acute lung injury in rats

目的探讨血管紧张素Ⅱ(AngⅡ)受体拮抗剂氯沙坦在大鼠内毒素性急性肺损伤(ALI)中的保护作用及可能机制。方法将50只雄性Wistar大鼠随机分为4组:对照组、脂多糖(LPS)组、LPS+氯沙坦组和LPS+氯沙坦+A779组。制备麻醉状态下静脉注射LPS致大鼠ALI模型,并予氯沙坦或血管紧张素1-7[Ang(1-7)]拮抗剂A779干预。前3组均于注射后1、4、6 h进行观察,后1组于4 h观察,每个时间点观察5只大鼠。BCA法测定肺泡灌洗液和血清蛋白量,苏木素-伊红(HE)对右肺中叶病理染色并评分,ELISA法检测血清AngⅡ、Ang(1-7)变化。结果光镜下可见大鼠出现特征性ALI病理改变。与对照组相比,LPS组血清AngⅡ含量1 h、4 h时升高(P<0.01),血清Ang(1-7)含量1 h时降低、4 h时升高(P均<0.01)。与LPS组相比,LPS+氯沙坦组大鼠肺损伤程度减轻,病理评分下降(P<0.01)。结论氯沙坦主要通过调节Ang(1-7)水平对大鼠内毒素性ALI起保护作用。

Objective To investigate the protective effect and possible mechanism of losartan,an angiotensin Ⅱ （AngⅡ）receptor antagonist,on endotoxin-induced acute lung injury （ALI）in rats.Methods Fifty male Wistar rats were randomly divided into four groups：control group,lipopolysaccharide （LPS）group,LPS ＋losartan group,and LPS ＋losartan ＋A779 group.ALI models of rats were established by intravenous injection of LPS under anesthesia state then intervented with losartan or A779,which is an antagonist of angiotensin 1-7[Ang （1-7）].The former three groups were observed at 1,4 and 6 h and the fourth group was observed at 4 h,with 5 rats at each time point.Proteins derived from bronchial alveolar lavage fluid （BALF）and serum were measured by BCA method.The pathological changes in the middle of the right lung tissue were observed with hematoxylin-eosin （HE）staining and the pathological scores were ob-tained.The contents of AngII and Ang （1-7）in serum were assessed by ELISA.Results The characteristiclly pathologi-cal changes in rats could be observed under optical microscope.Compared with control group,the contents of serum AngII at 1 h and 4 h in LPS group increased （P 〈0.01）;the content of serum Ang （1-7）at 1 h in LPS group decresed,butnbsp;at 4 h increased （all P 〈0.01）.Compared with LPS group,the lung injury alleviated in LPS ＋losartan group and the pathological score decreased （P 〈0.01）.Conclusion Losartan has a protective effect,which depends largely on regu-lating the level of Ang （1-7）,on endotoxin-induced ALI in rats.