福新普利和依普利酮对心肌梗死大鼠的心肌保护作用和心肌OPN表达的影响

The effects of myocardium of osteopontin expression of ACEI and aldosterone receptor antagonist in rats with myocardial infarction

目的观察血管紧张素转化酶抑制剂(ACEI)及醛固酮受体拮抗剂对心肌梗死大鼠的心肌保护作用和心肌骨桥蛋白(OPN)表达的影响。方法建立心梗大鼠模型,存活24 h的大鼠随机分为模型组(生理盐水,5mL/d)、福新普利组(灌胃10 mg/d)、依普利酮组(灌胃10 mg/d)和联合用药组(福新普利5 mg/d+依普利酮5mg/d),同时设假手术组。药物治疗6周后测定血流动力学和心功能指标,病理分析心肌纤维化程度,RT-PCR测定非梗死区OPN的表达。结果 (1)心肌梗死大鼠心脏非梗死区OPN显著增加,而福新普利和依普利酮均能抑制OPN上调,且联合用药组抑制作用明显;(2)心肌梗死大鼠心功能显著下降;而福新普利组和依普利酮组大鼠心功能明显改善,以联合用药组最明显;(3)心肌梗死大鼠均出现明显的心肌纤维化,左室质量及左室质量体重比增加,但福新普利和依普利酮治疗能抑制心肌纤维化,降低左室质量及左室质量体重比,以联合用药组最明显。结论心肌梗死大鼠心功能明显受损,伴随有非梗死区OPN表达增加、后期心肌纤维化等。而ACEI和醛固酮受体拮抗剂均能显著改善心肌梗死大鼠心功能和心肌纤维化,且两者具有协同效应,两者的心肌保护作用可能与抑制心肌梗死后OPN表达有关。

Objective To investigate the cardioprotection of fosinopril and eplerenone and their influence on the osteopontin （OPN） in myocardium of rats with myocardial infarction （MI）. Methods Rats with myocardial infarction were divided into 4 groups： myocardial infarction group, fosinopril （F） group （10 mg/d） , eplerenone （E） group （10 mg/d） and F ＋ E group （fosinopril 5 mg/d ＋ eplerenone 5 mg/d）. Rats without myocardial infarction served as controls. After treatment for 6 weeks, the hemodynamies and heart function were detected ; while the myocardial fibrosis was evalua- ted by pathological examination. RT - PCR was employed to assess the mRNA expression of OPN in the non - infarction area. Results In the myocardial infarction group, the heart function was significantly compromised, with myocardial fi- brosis; which were reversed by fosinoprll and/or eplerenone. Meanwhile, the OPN expression was increased dramatically in MI, which was reversed by fosinopril and/or eplerenone. The combined treatment provide significantly better efficacy. Conclusion Fosinopril and eplerenone can exert synergistic effect to improve the heart function and compromise the myocardial fibrosis which may be attributed to the reduction in OPN expression in the heart of rats with MI.