替米沙坦对压力负荷过重所致心衰大鼠心肌ACE2和AT1R表达的影响

目的 探讨替米沙坦对压力负荷过重所致心衰大鼠血管紧张素Ⅱ(AngⅡ)、心肌血管紧张素Ⅱ1型受体(AT1R)、血管紧张素转化酶2(ACE2)及MAS蛋白表达的影响。方法 采用SD雄性大鼠通过腹主动脉缩窄术构建压力负荷性心肌肥厚致心力衰竭(HF)模型。将大鼠随机分为假手术对照组(n=12)、HF模型组(n=12)和替米沙坦干预组(n=12)。替米沙坦干预组每天给予替米沙坦连续8周,检测各组大鼠血流动力学参数、心脏指数、血浆AngⅡ含量、心肌中AT1R、ACE2和MAS蛋白的表达情况。结果 HF模型组心脏指数、血流动力学指标、血浆AngⅡ的含量及心肌AT1R、ACE2蛋白的表达明显升高(P<0.01),MAS蛋白表达明显下降(P<0.01);替米沙坦干预组心脏指数、血流动力学指标明显下降(P<0.01),血浆AngⅡ的含量及心肌AT1R蛋白的表达明显下降(P<0.01),而MAS和ACE2蛋白的表达明显升高(P<0.01)。结论 应用替米沙坦可明显改善HF大鼠心室重构,可能与AngⅡ和AT1R的下调,而MAS和ACE2的上调有关。

Effect of telmisartan on ACE2 expression in rat hearts with pressure overload-induced heart failure

AIM To study the effect of telmisartan on Ang II level,AT1 R,ACE2 and MAS protein expressions in overload-induced heart failure of rats. METHODS Male Sprague Dawley rats( weighing250 g) were used to construct the pressure overload-induced heart failure model through aortic stenosis surgery. Animals were randomly divided into three groups: sham control group( n = 12),heart failure model group( HF,n = 12) and telmisartan intervention group( n = 12). Hemodynamics,heart MASs index and left ventricular MASs index,circulating and cardiac levels of angiotensin II,ACE2,AT1 R and MAS protein expressions were evaluated at week 8. RESULTS The hemodynamic meters,HMI and LVMI in HF group,improved significantly compared with those in sham control group( P < 0. 01). Levels of Ang II,AT1 R and ACE2 protein increased significantly in HF group( P < 0. 01),whereas MAS protein expressions decreased significantly compared with those in sham control group( P < 0. 01). The hemodynamic meters,HMI and LVMI in telmisartan group,were significantly lower than those in HF group( P < 0. 01). Levels of Ang II and AT1 R protein expressions were significantly lower in telmisartan group( P < 0. 01),whereas MAS and ACE2 protein expressions were significantly higher compared with those in the HF group( P < 0. 01). CONCLUSION Both downregulation of Ang II-ACE-AT1 axis and upregulation of Ang( 1-7)-ACE2-MAS axis may be involved in reversal of myocardial remodeling in heart failure by telmisartan.