上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（基础研究） • 上一篇    下一篇

重组血管紧张素转换酶2对ApoE基因缺陷小鼠肾脏caspase信号及细胞凋亡的影响

张振洲1，徐 冉1，常 青1，徐颖乐1，金海燕1,2，陈来江1，宋 蓓1，钟久昌1   

  1. 1.上海交通大学 医学院附属瑞金医院医学基因组学国家重点实验室，上海市高血压研究所，上海 200025；2. 上海交通大学 医学院附属瑞金医院临床心理科，上海 200025
  • 出版日期:2016-08-29 发布日期:2016-08-31
  • 通讯作者: 钟久昌，电子信箱：jiuchangzhong@aliyun.com。
  • 作者简介:张振洲（1988—），男，博士生；电子信箱：zhangbochuan1227@163.com。
  • 基金资助:

    国家重大研究计划（91339108）；国家重点基础研究发展计划（2014CB542300）；国家自然科学基金（81370362，81170246）；上海市教育委员会高峰高原学科建设计划（20152509）

Effects of recombinant angiotensin-converting enzyme 2 on renal caspase signaling and apoptosis in apolipoprotein E-deficient mice

ZHANG Zhen-zhou1, XU Ran1, CHANG Qing1, XU Ying-le1, JIN Hai-yan1,2, CHEN Lai-jiang1, SONG Bei1, ZHONG Jiu-chang11   

  1. 1.State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai Institute of Hypertension, Shanghai 200025, China; 2. Department of Mental Health, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
  • Online:2016-08-29 Published:2016-08-31
  • Supported by:

    National Major Research Plan Training Program， 91339108；National Basic Research Program of China，2014CB542300；National Natural Science Foundation of China，81370362，81170246；Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support，20152509

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摘要：

目的·探讨载脂蛋白E（ApoE）基因敲除（KO）小鼠肾脏caspase信号和凋亡水平的改变以及重组血管紧张素转换酶2（ACE2）干预治疗对其的影响。方法·采用11～12周龄的ApoEKO小鼠，每日经微泵输入1.5 mg/kg血管紧张素Ⅱ（Ang Ⅱ）和/或2 mg/kg重组人ACE2（rhACE2）治疗，为期2周。分别采用蛋白质印迹法和TUNEL法检测小鼠肾脏组织中细胞凋亡及相关信号改变。结果·与野生型对照组相比，ApoEKO小鼠肾脏细胞凋亡水平升高。Ang Ⅱ输入后促使ApoEKO小鼠收缩压水平升高，肾脏细胞凋亡水平、活化型caspase-3和caspase-8表达以及血浆尿素氮与肌酐水平均明显升高，上述作用可被重组ACE2干预所逆转。结论·重组ACE2治疗在降低Ang Ⅱ输入的ApoEKO小鼠血压水平的同时，可明显改善肾脏细胞凋亡和肾功能，提示ACE2对动脉粥样硬化性肾脏损伤具有一定的功效。

关键词: 血管紧张素转换酶2, 载脂蛋白E, 高血压, 细胞凋亡, 肾脏保护

Abstract:

Objective · To investigate the alterations in renal caspase signaling and apoptosis in apolipoprotein E (ApoE)-knockout (KO) mice and the effects of recombinant angiotensin-converting enzyme 2 (rACE2) on these alterations. Methods · The ApoEKO mice aged 11- or 12-week were infused with 1.5 mg/kg of Ang Ⅱ and/or 2 mg/kg of recombinant ACE2 (rACE2) per day for 2 weeks. Alterations in renal caspase signaling and renal cell apoptosis were determined with Western blotting and TUNEL method, respectively. Results · The renal cell apoptosis level was elevated in the ApoEKO mice as compared with the wild-type controls. Ang Ⅱ infusion promoted the increases in systolic blood pressure, renal cell apoptosis, expressions of cleaved caspase-3 and cleaved caspase-8, and levels of plasma urea nitrogen and creatinine, which could be revered by rACE2 intervention. Conclusion · The rACE2 treatment can lower the elevated blood pressure induced by Ang Ⅱ in ApoEKO mice and significantly improve renal cell apoptosis and kidney function, which suggest that ACE2 has certain protective effect on atherosclerotic renal injury.

Key words: angiotensin-converting enzyme 2, apolipoprotein E, hypertension, apoptosis, renoprotection