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山东大学学报（医学版） ›› 2015, Vol. 53 ›› Issue (2): 6-11.doi: 10.6040/j.issn.1671-7554.0.2014.658

• 基础医学 • 上一篇    下一篇

氯沙坦对大鼠内毒素性急性肺损伤的影响及可能机制

刘雷雷, 鞠云飞, 许文飞, 鞠远荣   

  1. 山东大学附属省立医院外科重症监护室, 山东 济南 250012
  • 收稿日期:2014-09-28 出版日期:2015-02-10 发布日期:2015-02-10
  • 通讯作者: 鞠远荣. E-mail:ju66157@126.com E-mail:ju66157@126.com
  • 基金资助:
    山东省科技发展计划(2011GGH21820;2011GGH21837)

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

LIU Leilei, JU Yunfei, XU Wenfei, JU Yuanrong   

  1. Department of Surgical Intensive Care Unit, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250012, Shandong, China
  • Received:2014-09-28 Online:2015-02-10 Published:2015-02-10

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摘要： 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.

关键词: 血管紧张素Ⅱ受体拮抗剂,氯沙坦, 血管紧张素1-7, 急性肺损伤/急性呼吸窘迫综合征

Abstract: 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 obtained. The contents of AngII and Ang (1-7) in serum were assessed by ELISA. Results The characteristiclly pathological 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, butat 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 regulating the level of Ang (1-7), on endotoxin-induced ALI in rats.

Key words: Angiotensin II receptor antagonist, losartan, Acute lung injury/Acute respiratory distress syndrome, Angiotensin 1-7

中图分类号: 

  • R563
[1] Phua J, Badia JR, Adhikari NKJ, et al. Has mortality from acute respiratory distress syndrome decreased over time?: a systematic review[J]. Am J Respir Crit Care Med, 2009, 179(3):220-227.
[2] Piper A, Song Y, Eves ND, et al. Year in review 2013: acute lung injury, interstitial lung diseases, sleep and physiology[J]. Respirology, 2014, 19(3):428-437.
[3] Cai B, Deitch EA, Ulloa L. Novel insights for systemic inflammation in sepsis and hemorrhage[J]. Mediators Inflamm, 2010: 642462-642462. doi: 10.1155/2010/642462.
[4] 张泓,孙耕耘.血管紧张素Ⅱ及其受体拮抗剂对大鼠肺微血管内皮炎性损伤效应的影响[J].中国危重病急救医学, 2004, 16(10):608-610. ZHANG Hong, SUN Gengyun. Inflammatory injurious effect of angiotensin II on pulmonary microvascular endothelium in rat[J]. Chinese Critical Care Medicine, 2004, 16(10):608-610.
[5] Shen L, Mo H, Cai L, et al. Losartan prevents sepsis-induced acute lung injury and decreases activation of nuclear factor kappaB and mitogen-activated protein kinases[J]. Shock, 2009, 31(5):500-506.
[6] Liu L, Qiu HB, Yang Y, et al. Losartan, an antagonist of AT1 receptor for angiotensin II, attenuates lipopolysaccharide-induced acute lung injury in rat[J]. Arch Biochem Biophys, 2009, 481(1):131-136.
[7] Wosten-van Asperen RM, Lutter R, Specht PA, et al. Acute respiratory distress syndrome leads to reduced ratio of ACE/ACE2 activities and is prevented by angiotensin-(1-7) or an angiotensin II receptor antagonist[J]. J Pathol, 2011, 225(4):618-627.
[8] Imanaka H, Shimaoka M, Matsuura N, et al. Ventilator-induced lung injury is associated with neutrophil infiltration, macrophage activation, and TGF-beta 1 mRNA upregulation in rat lungs[J]. Anesth Analg, 2001, 92(2):428-436.
[9] Matute-Bello G, Frevert CW, Martin TR. Animal models of acute lung injury[J]. Am J Physiol Lung Cell Mol Physiol, 2008, 295(3):L379-L399.
[10] Chen H, Bai C, Wang X. The value of the lipopolysaccharide-induced acute lung injury model in respiratory medicine[J]. Expert Rev Respir Med, 2010, 4(6):773-783.
[11] 陆立仁,张良清.内毒素致急性肺损伤发病机制研究进展[J].医学综述, 2010, 16(2):170-173. LU Liren, ZHANG Liangqing. Development on pathogenesis of lipopolysaccharide-injuced acute lung injury[J]. Medical Recapiculate, 2010, 16(2):170-173.
[12] 黄继义,刘才文,林建东,等.内毒素急性肺损伤TLR4-LPS信号传导对NF-κB活性的影响[J].临床肺科杂志, 2014, 19(2):223-226. HUANG Jiyi, LIU Caiwen, LIN Jiandong, et al. Influence of LPS-TLR4 signal transduction pathway on NF-κB in endotoxin-induced acute lung injury[J]. Journal of Clinical Pulmonary Medicine, 2014, 19(2):223-226.
[13] 刘韧,肖南,田昆仑,等.中性粒细胞凋亡延迟在脂多糖所致大鼠急性肺损伤发病机制中的作用[J].中华医学杂志, 2001, 81(10):617-621. LIU Ren, XIAO Nan, TIAN Kunlun, et al. The inflammatory mediators induced endothelial cell injury through delay neutrophils apoptosis[J]. Natl Med J China, 2001, 81(10):617-621.
[14] 马李杰,李王平,金发光,等.急性肺损伤/急性呼吸窘迫综合征发病机制的研究进展[J].中华肺部疾病杂志(电子版), 2013, 6(1): 65-68. doi:10.3877/cma.j.issn.1674-6902.2013.01.015.
[15] Souza LL, Costa-Neto CM. Angiotensin-(1-7) decreases LPS-induced inflammatory response in macrophages[J]. J Cell Physiol, 2012, 227(5):2117-2122.
[16] Simes e Silva AC, Silveira KD, Ferreira AJ, et al. ACE2, angiotensin-(1-7) and Mas receptor axis in inflammation and fibrosis[J]. Br J Pharmacol, 2013, 169(3):477-492.
[17] Gwathmey TM, Pendergrass KD, Reid SD, et al. Angioitensin-(1-7)-angiotensin-converting enzyme 2 attenuates reactive oxyen species formation to angiotensin II within the cell nucleus[J]. Hypertension, 2010, 55(1):166-171.
[18] Mccollun LT, Gallagher PE, Ann-tallant EA, et al. Angiotensin-(1-7) attenuates angiotensin II-induced cardiac remodeling associated with upregulation of dual-specifity phosphatase 1[J]. Am J Physiol Heart Circ Physiol, 2012, 302(3):H801-H810.
[19] Gome ER, Lara AA, Almeida PW, et al. Angiotensin-(1-7) prevevent cardiomyocyte pathological remodeling through a nitrc oxide/guanosine 3',5'cyclicmonophosphate-dependent pathway[J]. Hypertension, 2010, 55(1):153-160.
[20] Durik M, Van Veghel R, Kuiper A, et al. The effect of the thioether-bridged, stabilized Angiotensin-(1-7) analogue cyclic ang(1-7)on cardiac remodeling and endothelial function in rats with myocardial infarction[J]. Int J Hypertens, 2012: 536426.doi:10.1155/2012/536426.
[21] El-Hashim AZ, Renno WM, Raghupathy R, et al. Angiotensin-(1-7) inhibits allergic inflammation, via the MAS1 receptor, through suppression of ERK1/2-and NF-kB-dependent pathways[J]. Br J Pharmacol, 2012, 166(6):1964-1976.
[22] Iwai M, Horiuchi M. Devil and angel in the renin-angiotensin system: ACE-angiotensin Ⅱ-AT1 receptor axis vs. ACE2-angiotensin-(1-7)-Mas receptor axis[J]. Hypertens Res, 2009, 32(7):533-536.
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