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

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

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。

AIM To study the effect of telmisartan on AngII level, AT1 R, ACE2 and MAS protein expressions in overload-induced heart failure of rats. METHODS Male Sprague Dawley rats （weighing 250 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, AT1R 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 ）. Lev- els of AngII, AT1R 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 AngII and AT1R protein expressions were significandy 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 AngII-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.