Liu Yan, Liu Kunshen
Department of Geriatrics, The First Hospital of Shijiazhuang City, Shijiazhuang, Hebei 050011, P.R. China.
Department of Cardiology, The First Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei 050031, P.R. China.
Exp Ther Med. 2014 Sep;8(3):978-982. doi: 10.3892/etm.2014.1791. Epub 2014 Jun 18.
The aim of the present study was to investigate the effects of spironolactone and losartan on the early healing stage of acute myocardial infarction (AMI) in rats. An AMI rat model was established and the rats were randomly divided into four groups: AMI (n=12), AMI + spironolactone (AMI + S; n=12), AMI + losartan (AMI + L; n=12) and AMI + spironolactone combined with losartan (AMI + S + L; n=12). Sham-operated rats served as a control group (n=12). The expression levels of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in the non-infarcted myocardium surrounding the AMI area were determined using immunohistochemistry. In addition, the capillary density in the non-infarcted myocardium surrounding the AMI area was detected. The capillary densities around the infarcted area in the AMI and treatment groups at day 7 and 14 following AMI surgery were significantly higher compared with the sham-operated rats. Compared with the AMI group, the capillary densities around the infarcted area and the ratio of MMPs/TIMP-1 were increased in the treatment groups following AMI surgery; however, the increased ratio of MMPs/TIMP-1 was reduced at day 14 following AMI surgery. Therefore, these results indicated that spironolactone and losartan may promote the formation of collateral circulation in the non-infarcted tissue surrounding the infarcted area by regulating the production of MMPs.
本研究的目的是探讨螺内酯和氯沙坦对大鼠急性心肌梗死(AMI)早期愈合阶段的影响。建立了AMI大鼠模型,并将大鼠随机分为四组:AMI组(n = 12)、AMI + 螺内酯组(AMI + S;n = 12)、AMI + 氯沙坦组(AMI + L;n = 12)和AMI + 螺内酯联合氯沙坦组(AMI + S + L;n = 12)。假手术大鼠作为对照组(n = 12)。采用免疫组织化学法测定AMI区域周围非梗死心肌中基质金属蛋白酶(MMPs)和基质金属蛋白酶组织抑制剂(TIMPs)的表达水平。此外,检测AMI区域周围非梗死心肌中的毛细血管密度。AMI手术第7天和14天时,AMI组和治疗组梗死区域周围的毛细血管密度显著高于假手术大鼠。与AMI组相比,AMI手术后治疗组梗死区域周围的毛细血管密度和MMPs/TIMP-1比值增加;然而,AMI手术后第14天时,MMPs/TIMP-1增加的比值降低。因此,这些结果表明,螺内酯和氯沙坦可能通过调节MMPs的产生促进梗死区域周围非梗死组织中侧支循环的形成。