CAJ | 학술논문

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 ／（μgprotein·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。
목적탐토록사탄대토동맥죽양경화반괴혈관긴장소전환매2（ACE2）적조절작용。방법건립신서란대백토동맥죽양경화모형，수궤수자표법분위단순고지사양조、록사탄조、록사탄＋A779조，매조9지，응용유홍 O 염색측반괴지질함량，면역조화분별측정반괴거서세포급 ACE2、Ang-（1-7）단백함량표체，병검측각조 ACE2활성。소유결과이균수±표준차표시，실험수거용SPSS 15．0통계연건진행통계분석，각조대백토동맥죽양경화조직 ACE2활성，다조간적균수비교사용방차분석，조간비교사용 t 검험。결과록사탄조[（2．66±0．19）U ／（μg protein·h）]급록사탄＋A779조[（2．57±0．17）U ／（μgprotein·h）]교고지조[（1．30±0．18）U ／（μg protein·h）]동맥죽양경화조직 ACE2활성명현증가（t ＝15．87，15．45；P ＜0．05），록사탄조지질함량[（2．92±2．41）％]급거서세포양성면적백분솔[（15．71±2．46）％]명현소우단순고지조[（30．47±1．83）％]、[（23．07±2．06）％]여록사탄＋A779조[（32．52±2．88）％]、[（22．91±2．11）％]，차이유통계학의의（t ＝7．49，7．68；균 P ＜0．05）、（t ＝6．88，6．67；균 P ＜0．05）。록사탄조동맥죽양경화반괴내 ACE2여Ang-（1-7）단백대량표체（0．2330±0．0291여0．2652±0．0234）비단순고지조（0．1194±0．0114여0．1580±0．01932）증가，차이유통계학의의（t ＝10．91，10．58；균 P ＜0．05）；록사탄＋A779조（0．2224±0．0168여0．2583±0．0236）비단순고지조증가，차이유통계학의의（t ＝15．22，9．85；균 P ＜0．05），단여록사탄조비교차이무통계학의의（t ＝0．95，0．63；P ＞0．05）。결론록사탄통과상조 ACE2，증가 ACE2활성，사Ang-（1-7）단백표체증다억제동맥죽양경화발생발전。
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.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 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 /(μg protein·h)]and Losartan +A779 group [(2.57 ±0.17) U /(μg protein·h)]than those in high-cholesterol group [(1 .30 ±0.1 8)U /(μg protein·h)],and there was significant difference(t =1 5.87,1 5.45;P <0.05).The lipid content and macrophage infiltration in losartian group[(22.92 ±2.4)% and (1 5.71 ±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 ±2.1 1 %)].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 ±0.01 68, 0.2583 ±0.0236 )] were significant higher than that in high-cholesterol group [(0.1 1 94 ±0.01 1 4, 0.1 580 ±0.01 932)].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.