摘要
目的研究急性心肌梗死（AMI）后醛固酮（Ald）激活对心室重塑的影响，评价西拉普利、安体舒通（SPI）对AMI后Ald激活及心室重塑的抑制作用，探讨Ald致心肌纤维化的可能机制。方法将AMI后24h存活的Wistar大鼠随机分配至梗死组（MI组）、西拉普利组（ACEI组）、安体舒通组（SPI组）、西拉普利＋SPI组（ACEI＋SPI组），假手术组（SHAM）作为对照。两周后，放射免疫法测定血浆Ald含量，逆转录-聚合酶链（RT-PCR）方法测定心肌醛固酮合酶（P450Ald）、Ⅰ型胶原、Ⅲ型胶原及AT1受体mRNA水平。结果MI组血浆Ald含量，心肌Ⅰ型胶原、Ⅲ型胶原、AT1受体mRNA表达均较SHAM组显著增加；ACEI组、SPI组、ACEI＋SPI组心肌Ⅰ型、Ⅲ型胶原以及AT1受体mRNA表达均显著低于MI组。结论AMI后循环和心肌Ald生成激活，促进MI后心室重塑，AT1受体可能参与该过程，西拉普利、安体舒通均可不同程度地抑制AMI后Ald激活及心室重塑。
Objective To investigate the role of activation of cardiac aldosterone in ventricular remodeling, and to evaluate the effect of Cilazapril, spironolactone （SPI） on synthesis of myocardial aldosterone and ventricular remodeling after AMI. Method At 24 hours after AMI established by ligation of the left anterior descending coronary artery, Wistar rats were divided into four groups randomly： untreated group （MI group）, ACEI （Cilazapril 1 mg·kg^-·d^-1 ）, SPI （ Spironolactone 80 mg·kg^-·d^-1 ）, and ACEI ＋ SPI （ Cilazapril plus Spimnolactone） treated groups. The administration of the drugs lasted for 2 weeks. Sham- operation rats served as controls （SHAM group）. The plasma concentration of aldosterone was measured by radioimmunoassay test. The mRNA expression of cardiac aldosterone, collagen type Ⅰ and Ⅲ , angiotemin Ⅱ type 1 receptor （ AT1 ） was measured using reverse transcription- polymerase chain reaction （RT- PCR） method. Results The plasma concentration of aldosterone, and mRNA levels of myocardial aldosterone, collagen type Ⅰ and Ⅲ, and AT1 receptor were significantly increased by comparison with sham - operated group （ P 〈 0.01 ）. Treatment with Cilazapril, and combination of Sipironolactone significantly reduced plasma concentration of aldosterone in rats with AMI （ P 〈 0.01 ）. Plasma concentration of aldosterone in SPI group was higher than that of other groups （ P 〈 0.01 ）. Each drug inhibited remarkably the mRNA expression of cardiac collagen and AT1 receptor （ P 〈 0.01 ）. Conclusions MI is associated with an increase in plasma concentration of aldosterone and production of myocardial aldosterone, which might be involved in postinfarcted ventricular remodeling. Cilazapril and Sipironolactone has added effect on preventing ventricular remodeling after AMI induced by the activation of aldosterone. AT1 receptor might be the target of aldosterone to induce myocardial fibrosis.
出处
《中华急诊医学杂志》
CAS
CSCD
2007年第7期726-729,共4页
Chinese Journal of Emergency Medicine
关键词
心肌梗死
心室重塑
胶原
醛固酮合酶
血管紧张素Ⅱ1型受体
Myocardial infarction
Ventricular remodeling
Collagen
Aldosterone synthase
Angiotensin Ⅱ type 1 receptor （AT1 receptor）
