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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 of losartan, an angiotensin Ⅱ (Ang Ⅱ) receptor antagonist, on endotoxin-induced acute lung injury (ALI) in rats and its possible mechanism. Methods Fifty male Wistar rats were randomly divided into 4 groups: control group, lipopolysaccharide (LPS) group, LPS + losartan group and LPS + losartan + A779 group. The rat model of LPS-induced ALI was established under anesthesia and losartan or angiotensin 1-7 [Ang (1-7)] antagonist A779 was administered. The first three groups were observed at 1, 4 and 6 h after injection, and the latter group at 4 h. Five rats were observed at each time point. The amount of BALF and serum protein were measured by BCA method. The hematoxylin and eosin (HE) was stained for the right middle lobe and scored. The changes of serum AngⅡ and Ang (1-7) were detected by ELISA. Results The pathological changes of ALI appeared in rats under light microscope. Compared with the control group, the serum levels of AngⅡ in LPS group increased 1 h, increased at 4 h (P <0.01), and decreased at 1 h and increased at 4 h (P <0.01). Compared with LPS group, LPS + losartan group alleviated lung injury and pathological score decreased (P <0.01). Conclusion Losartan can protect rat endotoxin ALI mainly through regulating Ang (1-7) level.