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ACE2 agonist DIZE alleviates lung injury induced by limb ischemia-reperfusion in mice

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Author:: No author available

Journal Title:: Acta Physiologica Sinica

Issue:: 2

DOI:: 10.13294/j.aps.2018.0029

Key Word:: 缺血再灌注;肺损伤;肾素-血管紧张素系统;血管紧张素转换酶;血管紧张素转换酶2;三氮脒

Abstract：本文旨在探讨血管紧张素转换酶2 (angiotensin converting enzyme 2,ACE2)激动剂三氮脒(diminazene aceturate,DIZE)对小鼠肢体缺血再灌注(limb ischemia-reperfusion,LIR)引发的急性肺损伤(acute lung injury,ALI)的作用.雄性8周龄野生型和人ACE2 (hACE2)转基因ICR小鼠随机分为:野生对照组(W组)、野生模型组(WL组)、野生模型DIZE干预组(WLD组)、hACE2转基因对照组(T组)、hACE2转基因模型组(TL组)和hACE2转基因模型DIZE干预组(TLD组),每组6只.采用常规止血带套扎双侧后肢的方法复制小鼠LIR模型.各DIZE干预组在LIR前预先腹腔注射DIZE (15 mg/kg),持续4周.LIR结束时,计算肺组织脏器系数和湿干质量比(wet/dry weight ratio,W/D);计数肺泡灌洗液细胞并检测蛋白浓度;HE染色后观察肺组织形态变化并进行病理损伤评分;用ELISA法测定肺组织中血管紧张素Ⅱ (angiotensin Ⅱ,Ang Ⅱ)和Ang (1-7)水平;用Westem blot 检测肺组织血管紧张素Ⅱ受体1(angiotensin Ⅱ type 1 receptor,AT1)和Mas受体蛋白表达变化.结果显示:(1)WL和TL组小鼠均有明显的肺损伤,TL组小鼠肺损伤轻于WL组,而DIZE可减轻WL和TL组小鼠肺损伤.(2) WL组小鼠肺组织Ang Ⅱ水平升高,Ang (1-7)水平降低,TL组小鼠这两种蛋白没有明显变化,而DIZE可降低WL和TL组Ang Ⅱ水平,升高WL组Ang (1-7)水平.(3) WL和TL组小鼠肺组织AT1和Mas受体蛋白表达升高,而DIZE可逆转WL和TL组AT1蛋白表达的变化,并进一步上调这两组Mas受体蛋白表达.以上结果提示,DIZE可能通过调控局部肺组织ACE2-Ang (1-7)-Mas轴改善肾素-血管紧张素系统稳态失衡,减轻LIR所致小鼠ALI,从而发挥保护作用.

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