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

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/(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。

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

ObjectiveTo 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. ResultsThe 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). 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.