氯沙坦对兔动脉粥样硬化斑块血管紧张素转换酶2的调节作用及意义

doi:10.3877/cma.j.issn.2095-655X.2014.02.013

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摘要

目的探讨氯沙坦对兔动脉粥样硬化斑块血管紧张素转换酶2（ACE2）的调节作用。方法建立新西兰大白兔动脉粥样硬化模型，随机数字表法分为单纯高脂饲养组、氯沙坦组、氯沙坦+A779组，每组9只，应用油红O染色测斑块脂质含量，免疫组化分别测定斑块巨噬细胞及ACE2、Ang(1-7)蛋白含量表达，并检测各组ACE2活性。所有结果以均数±标准差表示，实验数据用SPSS15.0统计软件进行统计分析，各组大白兔动脉粥样硬化组织ACE2活性，多组间的均数比较使用方差分析，组间比较使用t检验。结果氯沙坦组［(2.66±0.19)U/（μgprotein·h)］及氯沙坦+A779组［(2.57±0.17)U/（μgprotein·h）］较高脂组［(1.30±0.18)U/（μgprotein·h）］动脉粥样硬化组织ACE2活性明显增加（t=15.87，15.45;P<0.05），氯沙坦组脂质含量［(2.92±2.41)%］及巨噬细胞阳性面积百分率［（15.71±2.46)%］明显少于单纯高脂肪［(30.47±1.83)%］、［(23.07±2.06)%］与氯沙坦+A779组［(32.52±2.88)%］、［(22.91±2.11)%］，差异有统计学意义（t=7.49，7.68；均P<0.05）、（t=6.88，6.67；均P<0.05）。氯沙坦组动脉粥样硬化斑块内ACE2与Ang(1-7)蛋白大量表达(0.2330±0.0291与0.2652±0.0234)比单纯高脂组(0.1194±0.0114与0.1580±

0.01932）增加,差异有统计学意义（t=10.91，10.58；均P<0.05）；氯沙坦+A779组(0.2224±0.0168与0.2583±0.0236)比单纯高脂组增加，差异有统计学意（t=15.22，9.85；均P<0.05），但与氯沙坦组比较差异无统计学意义（t=0.95，0.63；P>0.05）。结论氯沙坦通过上调ACE2，增加ACE2活性，使Ang（1-7）蛋白表达增多抑制动脉粥样硬化发生发展。

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Abstract：

Objective To investigate the effect of losartan on angiotensin converting enzyme 2 (ACE2)activity and ACE2、Ang(1-7) protein level in rabbit atherosclerotic plaques and analyse its meaning.MethodsMale New Zealand White rabbits were constructed atherosclerosis models.The rabbits were randomly 3 groups:high cholesterol group，losartan group and losartan+A779 group.ACE2 activities were measured by enzymatic assay.The lipid content was evaluated by Oil red O stain,the proteins expression of ACE2、Ang(1-7) and macrophage infiltration were also detected by immunohistochemistry.The differences of the protein expression of ACE2 were compared with chisquare test and ttest.Results The ACE2 activity higher in losartan group ［(2.66±0.19)U/(μgprotein·h)］ and Losartan+A779 group ［(2.57±0.17)U/（μgprotein·h）］ than those in highcholesterol group ［(1.30±0.18)U/（μgprotein·h）］,and there was significant difference(t=15.87，15.45；P<0.05).The lipid content and macrophage infiltration in losartian group［(22.92±2.4)% and (15.71±2.46)% respectly］ were significantly lower than those of in highcholesterol group［(30.47±1.83）% and (23.07±2.06）%］ and in Losartan+A779 group［(32.52±2.88）% and (22.91±2.11%）］.The expression of ACE2 and Angiotensin(17) in losartan group［(0.2330±0.0291)，(0.2652±0.0234)］ and in losartan +A779 group［(0.2224±0.0168，0.2583±0.0236)］ were significant higher than that in highcholesterol group［(0.1194±0.0114，0.1580±0.01932)］.However, there was no difference between losartan group and losartan+A779 group (P>0.05).ConclusionThe results show that ACE2 activity and ACE2、Ang(1-7) protein are regulated in atherosclerotic plaque by losartan, which may play an important role in the treatment of AS,proterin and ACE2，Ang(1-7) protein.

收稿日期: 2013-12-16

基金资助:国家“973”基础研究资助项目(2013CB530700)；国家自然科学基金资助项目（81170207）

通讯作者: 董波，Email：dongbo1@medmail.com.cn

引用本文:

张月辉朱莉张永欢于庆涛周照丽李树英王晓玉张绪洪董波. 氯沙坦对兔动脉粥样硬化斑块血管紧张素转换酶2的调节作用及意义[J]. 中华诊断学电子杂志, 2014, 2(2): 121-126.
Zhang Yuehui，Zhu Li，Zhang Yonghuan，Yu Qingtao，Zhou Zhaoli，Li Shuying，Wang Xiaoyu，Zhang Xuhong，Dong Bo.. Effect and significance of losartan on the angiotensin converting enzyme 2 in therosclerotic plaques. zhzdx, 2014, 2(2): 121-126.

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