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目的:探讨不同剂量培哚普利对缺血性心功能障碍家兔心功能的影响。方法:采用结扎冠状动脉前降支的方法制作缺血性心功能障碍家兔模型。利用随机数字表法将30只家兔随机分为培哚普利大、小剂量组和心功能障碍组。大、小剂量组分别给予培哚普利生理盐水溶液(浓度分别为1 g/L、0.33 g/L)2 m L·kg~(-1)·d~(-1)灌胃;心功能障碍组给予等量生理盐水灌胃。4周后心脏超声测定心功能;real-time PCR检测血管紧张素转换酶2(angiotensin-converting enzyme 2,ACE2)和血管紧张素2型受体(angiotensin type 2 receptor,AT2R)mRNA表达;ELISA检测家兔血清血管紧张素(angiotensin,Ang)-(1-9)和Ang-(1-7)水平。结果:与心功能障碍组相比,不同剂量培哚普利均可改善心功能(P<0.01),大剂量培哚普利比小剂量培哚普利改善心功能的效果显著(P<0.05);心功能障碍家兔应用培哚普利后,血清Ang-(1-9)和Ang-(1-7)水平均增高(P<0.01),ACE2和AT2R mRNA表达均增加(P<0.01);与小剂量组相比,大剂量组心肌ACE2和AT2R mRNA表达均增高(P<0.01),血清Ang-(1-9)水平增高(P<0.05),血清Ang-(1-7)水平无明显增加。相关性分析发现,左室射血分数与血清Ang-(1-9)、ACE2及AT2R水平呈正相关关系(P<0.01),与血清Ang-(1-7)水平无相关关系。结论:大剂量培哚普利较小剂量培哚普利可以更有效改善缺血性心功能障碍家兔心功能,其心功能的改善可能与Ang-(1-9)水平增多,引起AT2R活化相关。
Objective: To investigate the effects of different doses of perindopril on cardiac function in rabbits with ischemic heart failure. Methods: A rabbit model of ischemic heart dysfunction was made by ligation of the anterior descending coronary artery. Thirty rabbits were randomly divided into large and small perindopril group and cardiac dysfunction group using random number table method. Large and small dose groups were administered with perindopril saline solution (concentration of 1 g / L, 0.33 g / L respectively) 2 mL · kg -1 · d -1; Obstacle group was given the same amount of saline gavage. Heart function was measured by echocardiography 4 weeks later. The mRNA expression of angiotensin-converting enzyme 2 (ACE2) and angiotensin type 2 receptor (AT2R) was detected by real-time PCR. Rabbit serum levels of angiotensin (Ang) - (1-9) and Ang- (1-7). RESULTS: Perindopril at different doses improved heart function (P <0.01) compared with patients with impaired heart function. The effect of high dose of perindopril on cardiac function improved with low dose of perindopril (P <0.05) (P <0.01), while the expression of ACE2 and AT2R mRNA increased (P <0.01) in rabbits with cardiac dysfunction after perindopril treatment. The levels of Ang- (1-9) and Ang- ). Compared with the low-dose group, the expressions of ACE2 and AT2R mRNA in the high-dose group were significantly increased (P <0.01) and the levels of serum Ang- (1-9) No significant increase in level. Correlation analysis showed that left ventricular ejection fraction was positively correlated with serum Ang-1-9, ACE2 and AT2R levels (P <0.01), but not with serum Ang- (1-7) levels. Conclusions: Perindopril at high dose can lower the cardiac function in rabbits with ischemic heart failure more effectively. The improvement of cardiac function may be related to the increase of Ang- (1-9) levels and the activation of AT2R Related.