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  

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

作　　者：张振洲[1] 徐冉[1] 常青[1] 徐颖乐[1] 金海燕[1,2] 陈来江 宋蓓[1] 钟久昌[1] 

机构地区：[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　　处：《上海交通大学学报（医学版）》2016年第8期1115-1120,共6页Journal of Shanghai Jiao tong University:Medical Science

基　　金：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)~~

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。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.

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 

分 类 号：R692[医药卫生—泌尿科学] R54[医药卫生—外科学]