生长因子-1诱骗寡核苷酸对大鼠颈总动脉球囊损伤后血小板源性生长因子-BB表达的影响

摘要

Objective To investigate the effects of Egr-1 decoy ODN on intimal hyperplasia after vascular balloon injury and to primarily study its mechanism of inhibiting neointimal hyperplasia.Methods The intimal injury model of left carotid artery in rats was established.96 male Wistar rats were randomly divided into four groups:sham-group,injury-only-group,scrambled decoy ODNs (SCR) group and treatment group.In each group,6 rats were killed on the 3rd,7th,14th,21st day after balloon injury.Changes in the hyperplasia of the arterial intima were evaluated by hematoxylin-eosin (HE) staining.Changes in the expression of Egr-1 and PDGT-BB were detected by Real-time RT-PCRand Western blot.Results ①The thickening of intima began on the day after injury,and became more significant on the 14th and 21st day.②The level of Egr-1 mRNA and protein began to increase on the 3rd day and peaked on the 21st day,PDGF-BB mRNA and protein began to increase on the 3rd day and peaked on the 14th day.③Compared with the SCR and Injury-only-groups,NH was decreased significantly in Egr-1 decoy ODNs-treated rats (P＜ 0.01).Conclusion Egr-1 decoy ODN may specifically inhibit Egr-1 expression,then inhibit the expression of PDGF-BB.Finally,it reduces neointimal thickness and intimal hyperplasia after vascular injury.%目的 探讨针对早期生长反应因子-1 (Egr-1)的诱骗性寡脱氧核苷酸(decoy ODN)对大鼠动脉损伤后内膜增生的影响和可能的机制.方法 制备大鼠颈动脉球囊损伤模型,将96只Wistar大鼠随机分为假手术组、单纯损伤组、杂码寡脱氧核苷酸(SCR)组和治疗组,每组24只.术后3、7、14、21 d处死动物,每组6只.应用HE染色、Real time RT-PCR和Western blot方法观察大鼠颈动脉球囊损伤后内膜增生情况、Egr-1和血小板源性生长因子-BB (PDGF-BB)的表达及Egr-1 decoy ODN对它们的影响.结果 ①内皮损伤后3d内膜增厚不明显,7d内膜开始增厚,14、21 d时内膜明显增厚.②Egr-1 mRNA和蛋白水平于术后3d开始升高,21 d时达到顶峰,而PDGF-BB的mRNA和蛋白水平均于3d开始升高,14 d时达到顶峰.③转染Egr-1 decoy ODN治疗后,在各个时间点内膜增厚程度减轻,与对照组比较,Egr-1和PDGF-BB表达明显减少,差异有高度统计学意义(P＜0.01).结论 Egr-1 decoy ODN可能是通过特异性抑制Egr-1的表达,进而抑制PDGF-BB的表达,达到减轻新生内膜厚度、从而减轻血管损伤后内膜增生的目的.