论著(基础研究)

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

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  • 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
张振洲(1988—),男,博士生;电子信箱:zhangbochuan1227@163.com。

网络出版日期: 2016-08-31

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

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  • 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 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

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。

本文引用格式

张振洲 徐冉 常青 徐颖乐 金海燕 陈来江 宋蓓 钟久昌 . 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[J]. 上海交通大学学报(医学版), 2016 , 36(8) : 1115 . DOI: 10.3969/j.issn.1674-8115.2016.08.002

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.

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