CAJ | 학술논문

目的：探讨血管紧张素转换酶（ACE）2对大鼠心肌梗死（MI）后心肌组织中血管紧张素Ⅱ（AngⅡ）的表达与心肌重塑的影响，进一步阐明氯沙坦对大鼠MI后心肌重塑的作用机制。 　　方法：将32只健康雄性SD大鼠随机分为假手术组、MI组、MI+氯沙坦小剂量组[MI+10 mg/（kg·d）]和MI+氯沙坦大剂量组[MI+20 mg/（kg·d）]，各组均8只，随后将MI组和氯沙坦组大鼠建立心尖部MI模型。术中检测梗死前后心电图变化情况。术后24 h开始灌胃给药，给药期1个月，给药结束后测大鼠的血流动力学指标，并取大鼠心尖部心室肌组织，测其重量，随后组织固定切片，苏木素伊红（HE）染色观察心肌组织病理改变情况，逆转录-聚合酶链反应（RT-PCR）法和蛋白印迹（Western Blot）法检测心肌组织ACE2和AngⅡ的mRNA和蛋白表达量。 　　结果：MI组左心室重量及左心室重量指数（LVMI）均明显高于假手术组（P<0.05），左心室射血分数（LVEF）明显低于假手术组（P<0.05），差异均有统计学意义；氯沙坦各组的上述指标均有所改善，呈剂量依赖性。病理结果显示， MI组大鼠梗死区域可见心肌细胞肿胀、破裂，间质增生，炎症细胞浸润明显；MI+氯沙坦大剂量组心肌细胞坏死少见，肿胀减轻；MI+氯沙坦小剂量组居中；假手术组心肌纤维排列规则，无病理改变。MI组心肌内AngⅡ的mRNA和蛋白表达量显著高于假手术组（P<0.05），给予氯沙坦后，表达量呈剂量依赖性下降。MI组心肌内ACE2的mRNA和蛋白的表达量均略高于假手术组（P<0.05），氯沙坦各组继续升高，呈剂量依赖性。 　　结论：氯沙坦可增加大鼠ACE2表达量，进而通过抑制心肌组织内AngⅡ表达来改善MI后的心室重塑。
목적：탐토혈관긴장소전환매（ACE）2대대서심기경사（MI）후심기조직중혈관긴장소Ⅱ（AngⅡ）적표체여심기중소적영향，진일보천명록사탄대대서MI후심기중소적작용궤제。 　　방법：장32지건강웅성SD대서수궤분위가수술조、MI조、MI+록사탄소제량조[MI+10 mg/（kg·d）]화MI+록사탄대제량조[MI+20 mg/（kg·d）]，각조균8지，수후장MI조화록사탄조대서건립심첨부MI모형。술중검측경사전후심전도변화정황。술후24 h개시관위급약，급약기1개월，급약결속후측대서적혈류동역학지표，병취대서심첨부심실기조직，측기중량，수후조직고정절편，소목소이홍（HE）염색관찰심기조직병리개변정황，역전록-취합매련반응（RT-PCR）법화단백인적（Western Blot）법검측심기조직ACE2화AngⅡ적mRNA화단백표체량。 　　결과：MI조좌심실중량급좌심실중량지수（LVMI）균명현고우가수술조（P<0.05），좌심실사혈분수（LVEF）명현저우가수술조（P<0.05），차이균유통계학의의；록사탄각조적상술지표균유소개선，정제량의뢰성。병리결과현시， MI조대서경사구역가견심기세포종창、파렬，간질증생，염증세포침윤명현；MI+록사탄대제량조심기세포배사소견，종창감경；MI+록사탄소제량조거중；가수술조심기섬유배렬규칙，무병리개변。MI조심기내AngⅡ적mRNA화단백표체량현저고우가수술조（P<0.05），급여록사탄후，표체량정제량의뢰성하강。MI조심기내ACE2적mRNA화단백적표체량균략고우가수술조（P<0.05），록사탄각조계속승고，정제량의뢰성。 　　결론：록사탄가증가대서ACE2표체량，진이통과억제심기조직내AngⅡ표체래개선MI후적심실중소。
Objective: To investigate the effect of losartan on angiotensin II (Ang II) expression and myocardial remodeling in myocardial infarction (MI) rats’ model. Methods: A total of 32 SD male rats were divided into 4 groups, Sham operation group, MI group, MI with losartan 10mg/(kg·d) group and MI with losartan 20mg/(kg·d). n=8 in each group. MI model was established and the electrocardiogram changes before and after MI were recorded, hemodynamic indexes were detected at 4 weeks after MI, pathological changes of myocardial tissue were examined by HE staining. The myocardial mRNA and protein expressions of ACE2 and Ang II were detected by RT-PCR and Western Blot analysis. Results: Compared with Sham operation group, MI group showed increased LVMI and decreased LVEF P<0.05;the above changes were getting better in both MI with losartan groups in a dose-dependent manner. The pathological examination presented that MI group had myocardial cell swelling, fracture, hyperplasia and inflammatory cell infiltration, those damages were less in MI with losartan groups in a dose-dependent manner, Sham operation group had no pathological changes. Compared with Sham operation group, the mRNA and protein expressions of Ang II were obviously higher in MI group, P<0.05 and the expressions were decreased in MI with losartan groups in a dose-dependent manner;the mRNA and protein expressions of ACE2 were slightly increased in MI group and the expressions were further increased in MI with losartan groups in a dose-dependent manner. Conclusion: Losartan could increase ACE2 expression and therefore, inhibit Ang II expression and improve the ventricular remodeling in MI rats’ model.