血管紧张素转化酶2(ACE2)对大鼠肾氧化应激损伤的保护作用及其机制  

Protective Effect and Mechanism of Angiotensin Converting Enzyme 2(ACE2) on Renal Oxidative Stress Injury in Rats

作　　者：王艳霞[1] 张伟[1] 韩东宁[1] 张源淑[1] 

机构地区：[1]南京农业大学农业部动物生理生化重点开放实验室,南京210095

出　　处：《农业生物技术学报》2011年第5期881-886,共6页Journal of Agricultural Biotechnology

基　　金：国家自然科学基金(No.30871838-A200850)资助

摘　　要：本研究以腹腔注射链脲佐菌素(STZ)制造大鼠(Rattus norregicus)肾脏氧化应激损伤模型,并每天皮下注射3.7×10-5mol/L的胰岛素溶液1mL进行干预,探讨血管紧张素转化酶2(ACE2)在高糖所致的肾脏氧化应激损伤中的保护作用及其可能的机制。30d后,所有大鼠断头处死,采集血清及肾脏组织。测定所用大鼠血清中糖基化终末产物(AGEs)、丙二醛(MDA)、超氧化物歧化酶(SOD)、血管紧张素Ⅱ(AngⅡ)、血管紧张素1-7(Ang1-7)含量和肾脏组织中ACE2及Ang1-7受体MasmRNA水平。结果表明,与对照组相比,高血糖组大鼠血清AGEs、MDA和AngⅡ含量均极显著升高(P<0.01),SOD和Ang1-7含量极显著下降(P<0.01);肾脏组织中ACE2mRNA表达极显著下调(P<0.01),MasmRNA表达极显著上调(P<0.01)。胰岛素治疗后,大鼠血清中AGEs和MDA含量极显著下降(P<0.01),血清SOD含量极显著升高(P<0.01);AngⅡ含量显著下降(P<0.05),Ang1-7含量显著升高(P<0.05);肾脏组织中ACE2及其受体MasmRNA表达均极显著上调(P<0.01)。实验结果提示,ACE2参与了高糖所致的肾脏氧化应激损伤的抗损伤过程,其机制可能是通过激活ACE2-Ang(1-7)-Mas轴,减少了AngⅡ的产生。The objective of this study was to investigate the protective effect and mechanism of angiotensin converting enzyme 2（ACE2） on renal oxidative stress injury induced by high glucose. The rats（Rattus norregicus） model of renal oxidative stress injury was established by intraperitoneal injection of streptozotocin（STZ） solution, and treated by subcutaneous injection of insulin once a day（1 mL （3.7×10-5 mol/L））. After 30 days, all the rats were decapitated and the serum and kidney tissue were collected. The contents of advanced glycation end products （AGEs）, malondialdehyde（MDA）, superoxide dismutase（SOD）, angiotensinⅡ（AngⅡ）, angiotensin1-7（Ang1-7） in serum and the mRNA levels of ACE2 and Mas receptor in kidneys were measured. Compared with control group, the contents of AGEs, MDA and AngII in serum of high glucose rats were significantly increased（P〈0.01）, and the levels of SOD and Ang1-7 in serum were significantly decreased（P〈0.01）. The mRNA expression of ACE2 in kidneys was obviously reduced（P〈0.01）, while the mRNA expression of Mas was obviously raised（P〈0.01）. After insulin treatment, the contents of AGEs and MDA in serum were obviously reduced（P〈0.01）; the activity of SOD in serum was significantly raised（P〈0.01）; the level of AngII in serum was significantly decreased（P〈0.05） while the concentration of Ang1-7 in serum was significantly increased（P〈0.05）. The mRNA expression levels of ACE2and Mas receptor in kidneys were significantly increased（P〈0.01）. Exparemental results suggest that ACE2 plays an important role on the renal oxidative stress injury induced by high glucose and the mechanism may be that the activation of the ACE2-Ang1-7-Mas axis reduces the effect of AngⅡ.

关 键 词：血管紧张素转化酶2(ACE2) 大鼠 肾脏 氧化应激 保护作用 

分 类 号：Q51[生物学—生物化学]