关键词:  心肌缺血, CCAAT增强子结合蛋白质δ, 缺氧诱导因子1, 血红素加氧酶-1, 血管内皮生长因子A, C/ebp delta, 血管新生, 心肌保护

Abstract: Objective To investigate the therapeutic effect of adenoviral C/ebp delta vector on ischemic heart disease. Methods The Ad C / ebp delta-EGFP was constructed, and was injected into myocardium to observe the transductive efficiency to the cardiac myocytes. C57BL/6 mice were used in the experiments. The mice were divided into two groups: control group and experimental group. In control group, the Ad-EGFP was injected into myocardium. In experimental group, the Ad C/ebp delta-EGFP was injected into myocardium. The left anterior descending coronary artery was ligated after Ad C/ ebp delta-EGFP was injected into the left anterior wall of the left ventricle. The cardiac function of mice was examined by heart echocardiography. Mice were sacrificed without pain. The hearts were harvested, and the effect of C / ebp delta on myocardial apoptosis was observed with TUNEL staining. The effect of C/ebp delta on angiogenesis was performed by CD31 immunostaining. The effects of C/ ebp delta on the expressions of HIF-1, HO-1 and VEGF proteins in myocardium after myocardial infarction were detected by immunoblotting. Results The Ad C/ebp delta-EGFP was successfully constructed. The expression level of C/ebp delta in the myocardium was significantly higher in experimental group than that of control group. Local injection of adenoviral vector carrying C/ebp delta significantly improved LVFS (0.323±0.031 in experimental group versus 0.221±0.031 in control group, P＜0.05) and LVEF (0.605±0.085 in experimental group versus 0.464±0.071 in control group, P＜0.05). The myocardial cell apoptotic rate was significantly reduced in experimental group (20.36%± 3.07%) than that of control group (44.26%±6.25%, P＜0.01). The vascular density at the border area of myocardial infarction was increased (145.41±15.52 number of capillaries/per view in experimental group versus 77.60±5.19 number of capillaries/ per view in control group, P＜0.01) after heart infarction. The expressions of HIF-1, HO-1, and VEGF proteins were significantly increased in experimental group compared with those of control group (P＜0.01). Conclusion Adenoviral vector mediated C / ebp delta gene may activate HIF-1, which increases expressions of HO-1 and VEGF, resulting in protection of cardiomyocytes and promote angiogenesis in ischemic heart.

Key words:  myocardial ischemia, CCAAT-enhancer-binding protein-delta, hypoxia-inducible factor 1, heme oxygenase-1, vascular endothelial growth factor A, C/ebp delta,  angiogenesis, myocardial protection