坎地沙坦酯干预对AMI大鼠血管内皮功能及心肌ERK、CREB mRNA的影响

Interventional effects of Candesartan Cilexetil on vascular endothelial function and expressions of ERK/CREB mRNA in rats with acute myocardial infarction

目的探讨坎地沙坦酯(CAN)干预对大鼠急性心肌梗死(AMI)后内皮功能及梗死心肌胞外信号调节激酶(ERK)mRNA和cAMP反应元件结合蛋白(CREB)mRNA表达的影响。方法 30只动物被随机分为CAN组、假手术(Sham)组和AMI组。干预2周后,测量血压、血管紧张素Ⅱ(AngⅡ)、血一氧化氮合酶(NOS)、一氧化氮(NO)的水平、离体胸主动脉舒缩功能、梗死面积及ERK、CREB的mRNA在梗死区心肌中的表达水平。结果 AMI组较Sham组血浆AngⅡ水平显著升高、血清NO、NOS水平明显降低。同时内皮依赖性舒张(EDD)功能减退、梗死区心肌ERK、CREB的mRNA表达明显增加。CAN治疗后,血清NO、NOS水平升高至Sham组水平,同时升高血浆AngⅡ水平、缩小心肌梗死面积、降低梗死区心肌中ERK、CREB的mRNA表达,伴EDD功能明显改善,但组间血压并无明显差别。结论 CAN显著改善AMI后内皮功能紊乱(ED),缩小心肌梗死面积,降低AMI大鼠心肌ERK、CREBm RNA表达。

Objective To study the interventional effects of Candesartan Cilexetil on vascular endothelial function and expressions of ERK/CREB signaling pathway in rats with acute myocardial infarction.Methods 30 rats were randomized into CAN group,AMI group and Sham group.Two weeks after the treatment rats were sacrificed and blood pressure,levels of blood AngⅡ,NO and NOS,endothelial vasomotor effects of isolated thoracic aorta strips,myocardial infarctual area and the expressions of ERK mRNA and CREB mRNA in infarctual myocardium were explored.Results Blood AngⅡ levels were distinctly higher in AMI group when compared with the Sham group,while the NO and NOS level were much lower.accompanied with EDDs decreased seriously,and higher mRNA expressions of ERK1and CREB in infarctual myocardium.All of the above differences were significant.After the treatment of Candesartan Cilexetil,levels of serum NO and activities of NOS were obviously higher and almost reached the similar levels to those in Sham group,additionally endothelium-dependent diastole in isolated aortic strips improved greatly.Meanwhile Candesartan Cilexetil can not only increase the plasma AngⅡ,but also decrease the size of myocardial infarction and the mRNA expressions of ERK1 and CREB in infarctual myocardium significantly.However,blood pressure in all groups was not affected.Conclusion Candesartan Cilexetil can greatly improve the disordered endothelial function developing post-AMI,decrease the size of myocardial infarction and down-regulate the mRNA expressions of ERK and CREB in myocardium of infarctual zone.And all of the above protective effects of Candesartan Cilexetil were independent on blood pressure lowering.