早期生长应答因子-1在压力超负荷诱导的心肌肥厚及纤维化中的作用

摘要

目的通过早期生长应答因子-1基因敲除(EGR-1-/-)小鼠研究其在压力超负荷诱导的心肌肥厚及心肌纤维化中的作用.方法将20只EGR-1-/-小鼠和20只EGR-1野生型(EGR-1+/+)小鼠分别随机分为模型组和假手术组(n=10),通过主动脉缩窄术建立小鼠心肌肥厚模型,运用超声检测评价手术4周后小鼠心功能,组织病理学方法评价心肌肥厚及纤维化程度,实时定量聚合酶链式反应在mRNA水平检测心肌肥厚标志物心钠肽、脑钠肽及心肌纤维化标志物Ⅰ、Ⅲ型胶原.结果主动脉缩窄术后4周,EGR-1-/-模型组与EGR-1+/+模型组相比,EGR-1-/-模型组小鼠心功能有关指标得到明显改善(P＜0.05,n=10),且心肌肥厚及纤维化有关指标显著降低(P＜0.05,n=10).结论EGR-1基因敲除后能显著降低心肌肥厚及纤维化的程度.%Objective To clarify the role of early growth response-1 ( EGR-1 ) gene in cardiac hypertrophy and fibrosis induced by chronic pressure overload.Methods Twenty EGR-1 knockout(EGR-1-/-) mice and twenty wild-type EGR-1 (EGR-1 +/+ ) mice were randomly divided into model group and sham group respectively( n = 10).Cardiac hypertrophy model was established through aortic banding surgery.Four weeks after the aortic banding operation, cardiac function of the mice were evaluated by ultrasonic diagnosis equipment, and the degree of cardiac hypertrophy and fibrosis were evaluated by histological detection.In addition, the markers of cardiac hypertrophy including brain natriuretic peptide and atrial natriuretic peptide, and fibrosis markers(collagen Ⅰ 、collagen Ⅲ ) were detected by real-time quantitative polymerase chain reaction (PCR) at the mRNA level.Results Four weeks after the aortic banding operation, the cardiac function of EGR-1-/- group were improved significantly (P ＜0.05, n = 10), and the degree of cardiac hypertrophy and fibrosis were significantly reduced(P ＜ 0.05, n = 10), compared with those of EGR-1 +/+ group.Conclusion The knockout of EGR-1 can obviously decrease the degree of cardiac hypertrophy and fibrosis.