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  

Effect and significance of losartan on the angiotensin converting enzyme 2 in therosclerotic plaques

作　　者：张月辉[1,2] 朱莉[1] 张永欢[1] 于庆涛[1] 周照丽[1] 李树英[1] 王晓玉[1] 张绪洪[1] 董波[1] 

机构地区：[1]山东大学附属省立医院心内科,济南250021 [2]南方医科大学附属深圳宝安医院重症医学科

出　　处：《中华诊断学电子杂志》2014年第2期37-41,共5页Chinese Journal of Diagnostics(Electronic Edition)

基　　金：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)

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SPSS 15.0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/(μg protein·h)]及氯沙坦+A779组[(2.57±0.17)U/(μg protein·h)]较高脂组[(1.30±0.18)U/(μg protein·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)%]明显少于单纯高脂组[(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,差异有统计学意义(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。Objective To investigate the effect of losartan on angiotensin converting enzyme 2 （ACE2）activity and ACE2,Ang-（1-7） protein level in rabbit atherosclerotie plaques and analyse its meaning. Methods Male 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 macropbage 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/（ μg protein · h） ] and Losartan ＋ A779 group [ （2.57 ± 0.17） U/（ μg protein · h） ] than those in high-cholesterol group [ （ 1.30 ± 0.18 ） U/（ μg protein · 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 ）. Conclusion The 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.

关 键 词：氯沙坦 血管紧张素类 肽基二肽酶A 动脉粥样硬化 

分 类 号：R543.5[医药卫生—心血管疾病]