目的:研究模拟高原缺氧环境下大鼠心脏血管紧张素转换酶2(ACE2)的变化规律及调节因素,初步探讨ACE2与高原心脏病的关系。方法:在低氧环境(模拟海拔5000 m高原、23h/d)下饲养成年雄性Sprague Dawley(SD)大鼠,并分为缺氧1、15、30d组,设立平原对照组;检测各组大鼠右心室ACE2活性,同时测定右心室功能、重量指数以及肺动脉压力变化。在此基础上,我们观察了卡托普利、尼群地平灌胃对慢性缺氧30d组大鼠右心室ACE2活性的影响。结果:缺氧30d组右心室ACE2 mRNA、蛋白表达显著上调,ACE2活性明显增加,同时伴明显心室肥厚及心功能显著升高。另外,卡托普利、尼群地平虽然显著降低了肺动脉压力以及心脏功能,但对ACE2活性无显著影响。结论:慢性高原缺氧环境促使心脏ACE2的表达与活性上调,提示ACE2可能与缺氧心脏结构功能变化有关;表达增加是缺氧环境中大鼠右心室ACE2活性升高的原因之一,而肺动脉高压可能并非是缺氧情况下ACE2活性变化的主要原因。
AIM: To determine the right ventricular angiotensin converting enzyme2 (ACE2) activity in adult SD rats under normoxia and hypoxia environment, and to detect the relationship between ACE2 and high altitude heart disease initially. METHODS: Adult male Sprague Dawley (SD) rats were raised under hypoxia environment simulated to high altitude (5 000 m, 23 h/d), then divided into hypoxia 1 d, 15 d and 30 d groups randomly. The control group was set up under normoxia environment. The right ventricular function, ponderal index, pulmonary artery pressure and right ventricular ACE2 activity were determined. The effect of captopril or nitrendpine on cardiac ACE2 activity in hypoxia 30 d group was also observed. RESULTS : The dramatic up - regulation of cardiac ACE2 expression of mRNA and protein and its activity in hypoxia 30 d group was observed, together with obvious increase in right ventricular function, ponderal index and pulmonary artery pressure. Although eaptopril or nitrendipine depressed pulmonary artery pressure and cardiac function dramatically, no significant alteration of right ventricular ACE2 activity was detected. CONCLUSION: Chronic hypoxie exposure promotes the ACE2 expression and activity in right ventricular, indicating that ACE2 may be correlated to the changes of cardiac architecture and function induced by hypoxia. Up - regulation of ACE2 expression maybe contribute to the increase in right ventricular ACE2 activity, and pulmonary artery hypertension may not be the main reason for the changes of ACE2 activity under hypoxia environment.