醛固酮通过调节ACE2-Ang(1-7)-Mas受体轴诱导内皮细胞凋亡的研究

醛固酮通过调节ACE2-Ang(1-7)-Mas受体轴诱导内皮细胞
凋亡的研究
张霞;潘瑜;金惠敏
【期刊名称】《上海交通大学学报（医学版）》
【年(卷),期】2013(033)001
【摘要】目的探讨醛固酮对内皮细胞ACE2-Ang(1-7)-Mas受体轴的影响及其与凋亡的关系.方法将体外培养的人脐静脉内皮细胞(HUVEC)分为对照组(DMEM/F12培养基)、醛固酮组(10、100、1 000 nmol/L醛固酮干预)和醛固酮拮抗组(100 nmol/L醛固酮+1μmol/L醛固酮受体拮抗剂共同干预).采用免疫荧光细胞化学染色法观察细胞ACE2蛋白的表达；Western blotting检测细胞中ACE2和Mas受体的表达；酶联免疫吸附实验(ELISA)检测细胞培养上清中AngⅡ和Ang(1-7)蛋白的含量以及凋亡相关蛋白caspase-3的活性；流式细胞术结合FITC-Annexin V/PI荧光染色检测细胞凋亡.结果与对照组比较,醛固酮组细胞ACE2和Mas受体的表达明显下调(P＜0.01),并呈浓度依赖性.在100 nmol/L醛固酮组,随着干预时间的延长,细胞ACE2和Mas受体的表达明显下调(P＜0.01),呈时间依赖性；而醛固酮拮抗组细胞ACE2和Mas受体的表达显著高于100 nmol/L 醛固酮组(P＜0.01).ELISA检测结果显示,随着干预时间的延长,醛固酮组细胞培养上清中AngⅡ浓度和caspase-3活性均显著升高,而Ang(1-7)浓度降低.流式细胞术检测结果显示:醛固酮组细胞凋亡率显著高于对照组,醛固酮拮抗组细胞凋亡率显著低于醛固酮组(P＜0.05).结论醛固酮具有调节ACE2-Ang(1-7)-Mas受体轴的作用,并可能通过此轴诱导内皮细胞凋亡.%Objective To investigate the effect of aldosterone on ACE2 - Ang ( 1 -7) - Mas receptor axis of endothelial cells,
and explore its association with apoptosis. Methods Human umbilical vein endothelial cells ( HUVEC) cultured in vitro were divided into control group ( DMEM/F12 culture medium), aldosterone group (treatment with 10, 100, 1 000 nmol/L aldosterone) and aldosterone antagonist group ( 100 nmol/L aldosterone + 1 μmol/L aldosterone antagonist) . The expression of ACE2 protein in cells was observed with immunofluorescence cytochemical staining, the expression of ACE2 receptor and Mas receptor was determined by Western blotting, the contents of AngII and Ang ( 1-7) protein and caspase-3 activity in the supernatant of culture fluid were measured by ELISA, and cell apoptosis was detected by flow cytometry with FITC-Annexin V/PI fluorescein staining. Results Compared with control group, the expression of ACE2 receptor and Mas receptor in cells in aldosterone group significantly decreased in a dose-dependent manner (P <0.01). In 100 nmol/L aldosterone group, the expression of ACE2 receptor and Mas receptor in cells significantly decreased in a time-dependent manner (P <0.01) , while the expression of ACE2 receptor and Mas receptor in cells in aldosterone antagonist group was significantly higher than that in 100 nmol/L aldosterone group (P <0.01). The content of Ang II and caspase-3 activity in the supernatant of culture fluid in aldosterone group significantly increased with the time, while the content of Ang (1-7) significantly decreased. The apoptosis rate in aldosterone group was significantly higher than that in control group, while the apoptosis rate in aldosterone antagonist group was significantly lower than that in aldosterone group ( P < 0. 05).Conclusion Aldosterone may regulate
ACE2 - Ang (1-7) - Mas receptor axis, which may play a role in inducingrnendothelial cell apoptosis.
【总页数】6页(P6-11)
【作者】张霞;潘瑜;金惠敏
【作者单位】上海交通大学医学院附属第三人民医院肾脏内科,上海201900;上海交通大学医学院附属第三人民医院肾脏内科,上海201900;上海交通大学医学院附属第三人民医院肾脏内科,上海201900
【正文语种】中文
【中图分类】R692
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