血管紧张素转化酶2(ACE2)在糖尿病大鼠肾损伤中的作用及机制分析

doi:10.7506/spkx1002-6630-201309058

食品科学 ›› 2013, Vol. 34 ›› Issue (9): 287-291.doi: 10.7506/spkx1002-6630-201309058

血管紧张素转化酶2(ACE2)在糖尿病大鼠肾损伤中的作用及机制分析

王珊珊，马畅，张伟，王艳霞，张源淑*

南京农业大学农业部动物生理生化重点开放实验室，江苏南京 210095

收稿日期:2013-01-19 修回日期:2013-04-15 出版日期:2013-05-15 发布日期:2013-05-07
通讯作者: 张源淑 E-mail:wangshanshan2544@126.com
基金资助:
国家自然科学基金项目(30871838 A200850)；江苏省普通高校研究生创新计划项目(CXZZ12-0296)

Effect and Mechanism of Angiotensin-converting Enzyme 2 on Diabetic Renal Injury in Rats

WANG Shan-shan，MA Chang，ZHANG Wei，WANG Yan-xia，ZHANG Yuan-shu*

Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China

Received:2013-01-19 Revised:2013-04-15 Online:2013-05-15 Published:2013-05-07
Contact: ZHANG Yuan-shu E-mail:wangshanshan2544@126.com

摘要/Abstract

摘要：

目的：通过比较肾脏组织中血管紧张素转化酶Ⅰ(angiotensin converting enzyme Ⅰ，ACE)-血管紧张素Ⅱ(ang iotensin Ⅱ，AngⅡ)-血管紧张素Ⅱ受体1亚型(Ang Ⅱ type 1 receptor，AT1)/血管紧张素转化酶2(angiotensinconverting enzymeⅡ，ACE2) -血管紧张素1-7(angiotensin 1-7，Ang 1-7)-Mas及肾素-血管紧张素系统(renin-angiotensinsystem，RAS)相关调节因子在肾损伤过程中的表达差异，探讨ACE2在糖尿病大鼠肾脏损伤发生发展中的作用及可能的分子机制。方法：研究选用STZ腹腔注射致大鼠糖尿病，分别于15d(对照1组和模型1组)和30d(对照2组和模型2组)断头处死，取肾脏组织。PCR检测肾脏组织中ACE、AT1、ACE2和Mas mRNA的表达水平；放免法测定肾脏局部组织中肾素活性和Ang I、AngⅡ含量。结果显示：与对照组相比，模型1组大鼠肾脏组织中ACE2 和其Mas受体mRNA表达升高，ACE mRNA表达无显著差异，AT1 mRNA表达下降，ACE/ACE2 mRNA比值下降；模型2组大鼠肾脏组织中ACE2 mRNA表达低于对照2组，Mas受体mRNA表达无显著变化，ACE mRNA的表达高于对照2组，AT1受体有同样升高趋势，ACE/ACE2 mRNA表达比值较对照2组升高，有显著性差异。放射免疫分析结果显示：模型1组肾脏局部组织中肾素活性和Ang I含量低于对照1组，有显著性差异(P＜0.05)，而AngⅡ含量高于对照1组，无显著性差异(P＞0.05)；模型2组肾素活性和Ang I极显著高于对照2组(P＜0.01)，同时AngⅡ也显著高于对照2组(P＜0.05)。结论：ACE与ACE2表达失调是糖尿病大鼠肾损伤发生发展的原因之一。损伤初期以ACE2-Ang(1-7)-Mas轴的激活占优势；严重损伤时，ACE-Ang Ⅱ-AT1轴的激活占优势。ACE2在早期肾脏病变的发病中通过降解AngⅡ发挥积极的保护作用。

关键词: ACE2, 糖尿病, 肾损伤, ACE-Ang Ⅱ-AT1轴, ACE2-Ang-(1-7)-Mas轴

Abstract:

Objective: To compare the expression levels of ACE- AngⅡ-AT1/ACE2- Ang1-7-Mas and related regulatory
factors involved in the RAS (renin–angiotensin system) in order to explore the role and mechanism of ACE2 in the
occurrence and development of diabetes-induced renal in rats. Methods: Diabetes was induced in rats by intraperitoneal
injection of streptozotocin (STZ). The rats in the control group 1 and the model group 1 were guillotined 15 d later, and those
in the control group 2 and the model group 2 were guillotined 30 d later for measurement of the renal expression lelvels of
ACE, AT1, ACE2 and Mas mRNA and determination of the contents of AngⅠ and AngⅡ in local renal tissues. Results:
Compared with the control groups, the expression levels of ACE2 and Mas receptor mRNA were elevated in the model
group 1, ACE mRNA expression showed no significant difference, while AT1 mRNA expression and ACE/ACE2 mRNA
ratio decreased; renal ACE2 mRNA expression was lower in the model group 2 than in the control group 2, no obvisous
difference in Mas receptor mRNA expression existed, whereas the expression of ACE mRNA and AT1 receptor presented
an increasing trend and the ACE/ACE2 mRNA ratio of the modle group 2 was higher than that of the control group 2 with a
significant difference. The model group 1 showed a decrease in renin activity and AngⅠ content in local renal tissues with
a signficant difference (P ＜ 0.05) but an increase in AngⅡ content with no significant difference (P ＞ 0.05) as compared
to the control group 1. Compared with the control group 2, extremely significantly higher levels (P ＜ 0.01) of renin activity
and AngⅠ content togeterh with a significant higher level (P ＜ 0.05) of AngⅡ were observed in the model group 2.Conclusion: Abnormal expression of ACE and ACE2 is one of the reasons for the occurrence and development of diabetesinduced
renal injury in rats. The ACE2-Ang (1-7)-Mas axis activation is dominant at the initial stage of renal injury, which
is replaced by the ACE-AngⅡ-AT1 shaft activation at the serious stage. ACE2 plays a protective role by degrading AngⅠ
against the incidence of early renal disease.

Key words: angiotensin converting enzymeⅡ(ACE2), diabetes, kidney injury, angiotensin converting enzymeⅠ(ACE)-AngⅡ-AT1 axis, angiotensin converting enzymeⅡ- Ang-(1-7)-Mas axis

中图分类号:

R933.7

王珊珊，马畅，张伟，王艳霞，张源淑*. 血管紧张素转化酶2(ACE2)在糖尿病大鼠肾损伤中的作用及机制分析[J]. 食品科学, 2013, 34(9): 287-291.

WANG Shan-shan，MA Chang，ZHANG Wei，WANG Yan-xia，ZHANG Yuan-shu*. Effect and Mechanism of Angiotensin-converting Enzyme 2 on Diabetic Renal Injury in Rats[J]. FOOD SCIENCE, 2013, 34(9): 287-291.

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血管紧张素转化酶2(ACE2)在糖尿病大鼠肾损伤中的作用及机制分析

Effect and Mechanism of Angiotensin-converting Enzyme 2 on Diabetic Renal Injury in Rats

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