Marques Fúlvia D, Melo Marcos B, Souza Leandro E, Irigoyen Maria Claúdia C, Sinisterra Rúben D, de Sousa Frederico B, Savergnini Sílvia Q, Braga Vinícius B A, Ferreira Anderson J, Santos Robson A S
National Institute of Science and Technology in Nanobiopharmaceutics, Federal University of Minas Gerais, 31.270-901 Belo Horizonte, MG, Brazil.
Int J Hypertens. 2012;2012:795452. doi: 10.1155/2012/795452. Epub 2012 Feb 9.
In this study was evaluated the chronic cardiac effects of a formulation developed by including angiotensin(Ang)-(1-7) in hydroxypropyl β-cyclodextrin (HPβCD), in infarcted rats. Myocardial infarction (MI) was induced by left coronary artery occlusion. HPβCD/Ang-(1-7) was administered for 60 days (76 μg/Kg/once a day/gavage) starting immediately before infarction. Echocardiography was utilized to evaluate usual cardiac parameters, and radial strain method was used to analyze the velocity and displacement of myocardial fibers at initial time and 15, 30, and 50 days after surgery. Real-time PCR was utilized to evaluate the fibrotic signaling involved in the remodeling process. Once-a-day oral HPβCD/Ang-(1-7) administration improved the cardiac function and reduced the deleterious effects induced by MI on TGF-β and collagen type I expression, as well as on the velocity and displacement of myocardial fibers. These findings confirm cardioprotective effects of Ang-(1-7) and indicate HPβCD/Ang-(1-7) as a feasible formulation for long-term oral administration of this heptapeptide.
在本研究中,评估了一种通过将血管紧张素(Ang)-(1-7)包合于羟丙基β-环糊精(HPβCD)中所开发的制剂对心肌梗死大鼠的慢性心脏影响。通过左冠状动脉闭塞诱导心肌梗死(MI)。在梗死前即刻开始给予HPβCD/Ang-(1-7)60天(76μg/千克/每天一次/灌胃)。利用超声心动图评估常规心脏参数,并采用径向应变法分析术后初始时间以及术后15、30和50天时心肌纤维的速度和位移。利用实时聚合酶链反应评估重塑过程中涉及的纤维化信号传导。每天一次口服HPβCD/Ang-(1-7)可改善心脏功能,并减少MI对转化生长因子-β(TGF-β)和I型胶原蛋白表达以及心肌纤维速度和位移所诱导的有害影响。这些发现证实了Ang-(1-7)的心脏保护作用,并表明HPβCD/Ang-(1-7)是该七肽长期口服给药的一种可行制剂。