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目的研究奥美沙坦酯对急性心肌梗死(acute myocardial infarction,AMI)大鼠的内皮功能和细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)/cAMP反应元件结合蛋白(cAMP response element binding protein,CREB)信号通路的干预。方法将40只大鼠随机分为AMI组、奥美沙坦酯低剂量(olmesartan medoxomil low dose,OML)组、奥美沙坦酯高剂量(olmesartan medoxomil high dose,OMH)组和假手术(Sham)组,干预2周后处死,检测血压,血NO、AngⅡ含量,NOS活性,离体胸主动脉条片舒缩功能,MI面积及梗死区心肌中ERK、CREB mRNA表达水平。结果与Sham组比较,AMI组血清NO含量、NOS活性降低,胸主动脉内皮依赖性舒张(endothelium-dependent diastole,EDD)功能减退,血浆AngⅡ含量升高,伴心肌组织ERK、CREB mRNA表达增加,差异有显著性。经奥美沙坦酯干预后,血清NO含量、NOS活性升高达Sham组水平,胸主动脉EDD显著改善,同时呈剂量依赖性升高血浆AngⅡ含量,缩小MI面积,降低ERK、CREB mRNA表达,而各组血压并无明显差异。结论奥美沙坦酯在不影响血压的前提下显著改善AMI后内皮功能紊乱(Endothelial dysfunction,ED),缩小MI面积,并可呈剂量依赖性降低AMI大鼠心肌ERK、CREB mRNA表达。
Objective To investigate the effects of olmesartan medoxomil on endothelial function and cAMP response element binding protein (ERK) / cAMP response element binding protein (cAMP response element binding protein) in acute myocardial infarction (AMI) CREB) signaling pathway. Methods Forty rats were randomly divided into AMI group, olmesartan medoxomil low dose (OML) group, olmesartan medoxomil high dose (OMH) group and sham operation group After 2 weeks intervention, blood pressure, blood level of NO, AngⅡ, NOS activity, systolic and diastolic function of isolated thoracic aortic strips, area of MI and expression levels of ERK and CREB mRNA in myocardial infarction area were detected. Results Compared with Sham group, serum NO content and NOS activity decreased, endothelium-dependent diastole (EDD) function decreased, plasma AngⅡ level increased, myocardial ERK and CREB mRNA increased, The difference was significant. After the intervention of olmesartan medoxomil, the serum NO and NOS activity increased to the level of Sham group and the EDA of thoracic aorta significantly improved, meanwhile, the content of AngⅡ in plasma increased, the area of MI decreased, and the expression of ERK and CREB mRNA decreased in a dose-dependent manner There was no significant difference in blood pressure between groups. Conclusion Olmesartan medoxomil can significantly improve endothelial dysfunction (ED), reduce the area of MI, and reduce the expression of ERK and CREB mRNA in AMI rats in a dose-dependent manner without affecting the blood pressure.