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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 regulatory effect of losartan on angiotensin-converting enzyme 2 (ACE2) in atherosclerotic plaques in rabbits. Methods Atherosclerosis model was established in New Zealand white rabbits. Random number table was divided into three groups: high fat diet group, losartan group and losartan + A779 group, with 9 in each group. Content and immunohistochemistry were used to detect the protein expression of ACE2 and Ang- (1-7) in macrophages and ACE2 activity in each group. All the results were expressed as mean ± standard deviation, the experimental data were statistically analyzed with SPSS 15.0 statistical software, ACE2 activity in atherosclerotic tissue of each group, the mean of multiple groups were compared using ANOVA, t-test was used to compare between groups . Results Compared with high fat group [(1.30 ± 0.19) U / (μg protein · h) and losartan + A779 group (2.57 ± 0.17 U / μg protein · h) in losartan group, 0.18) U / (μg protein · h)], the activity of ACE2 in atherosclerotic tissue was significantly increased (t = 15.87,15.45; P <0.05), the content of lipid in losartan group [(2.92 ± 2.41)%] (15.71 ± 2.46)%] was significantly lower than those in losartan + A779 group [(30.47 ± 1.83)%] and (23.07 ± 2.06)% in losartan + A779 group [(30.47 ± 1.83)%] ], And (22.91 ± 2.11)%, respectively, with significant difference (t = 7.49 and 7.68; all P <0.05) (t = 6.88 and 6.67, all P <0.05). Compared with hyperlipidemia group (0.1194 ± 0.0114 and 0.1580 ± 0.01932), the expression of ACE2 and Ang- (1-7) protein in atherosclerotic plaque in Losartan group were significantly increased (0.2330 ± 0.0291 and 0.2652 ± 0.0234) (T = 10.91,10.58; all P <0.05); losartan + A779 group (0.2224 ± 0.0168 and 0.2583 ± 0.0236) increased compared with the hyperlipidemia group, the difference was statistically significant (t = 15.22,9.85; All P <0.05), but no significant difference compared with losartan group (t = 0.95,0.63; P> 0.05). Conclusion Losartan up-regulates ACE2, increases ACE2 activity, and increases the expression of Ang- (1-7) protein to inhibit the development of atherosclerosis.