外源性血管紧张素Ⅱ在体灌注对大鼠肺泡屏障的损伤作用及机制
Journal Title: Di-er Junyi Daxue Xuebao - Year 2008, Vol 29, Issue 12
Abstract
目的:观察外源性血管紧张素(Ang)Ⅱ灌注大鼠气道对肺上皮屏障的损伤作用,并探讨其可能的损伤机制。方法:Wistar大鼠随机分为5组:PBS对照组、Ang 6、20 h组、Ang+zVAD-fmk组、Ang+氯沙坦组(n=10),各组大鼠分别经气管灌注PBS、Ang(10 μmol/L)磷酸盐缓冲溶液、Ang(10 μmol/L)+zVAD-fmk(60 μmol/L)、Ang+氯沙坦(losartan,100 μmol/L),另设10只大鼠不作任何处理作为空白对照组。大鼠经气管灌入相应溶液后在体灌洗动物肺脏,测定灌洗液中的血红蛋白(Hb)和灌洗肺前由静脉注入的荧光物质(BODIPY)标记的白蛋白含量,判断肺损伤；取肺组织标本进行病理学观察；采用末端脱氧核苷酸转移酶标定法(TUNEL)和抗caspase 3免疫标定方法检测肺泡上皮细胞凋亡。结果:灌注Ang 6 h后,支气管和肺泡上皮细胞内标定的断裂DNA片段(P<0.05)和活性caspase 3(P<0.01)显著增加,但单纯灌注磷酸盐缓冲溶液没有作用；同时灌注caspase抑制剂zVAD-fmk或Ang受体1阻断剂氯沙坦均阻断Ang对DNA 和caspase 3的作用。灌注Ang 6 h后,肺泡灌洗液中荧光标定的白蛋白含量(P<0.01)和Hb含量(P<0.05)亦显著增加；zVAD-fmk或氯沙坦亦阻断支气管肺泡灌洗液中荧光白蛋白含量和Hb含量的变化。结论:在体大鼠呼吸道内灌注外源性Ang可介导肺泡上皮细胞凋亡；Ang诱导的在体肺泡上皮细胞凋亡可能与Ang受体1亚型介导的激活caspase 3信号转导通路有关。
Authors and Affiliations
Jia-ju ZHUANG
Keywords
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外源性血管紧张素Ⅱ在体灌注对大鼠肺泡屏障的损伤作用及机制
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