摘要
目的观察局部转染早期生长反应因子-1(early growth response factor-1,Egr-1)的诱骗性寡脱氧核苷酸(decoy oligodeoxynucleotides,decoy ODNs)对球囊损伤颈总动脉后内膜增生及细胞内细胞黏附分子-1(intercellular adhesion molecule-1,ICAM-1)表达的影响,并初步探讨Egr-1 decoy ODNs抑制球囊损伤后内膜增生的机制。方法 96只健康雄性Wistar大鼠随机分为假手术组、单纯损伤组、杂码寡脱氧核苷酸(scrambled decoy ODNs,SCR)组和Egr-1 decoy ODNs组,每组24只。术后3、7、14及21 d处死动物,每组6只。应用HE染色、Real time RT-PCR和Western-blotting方法观察大鼠颈动脉球囊损伤后内膜增生情况、Egr-1和ICAM-1的表达及Egr-1 decoy ODNs对它们的影响。结果①内皮损伤后3 d内膜增厚不明显,7d内膜开始增厚,14 d和21 d时内膜明显增厚。②Egr-1mRNA和蛋白水平于术后3 d开始升高,21 d时达到顶峰,而ICAM-1的mRNA和蛋白水平均于术后3 d开始升高,7 d达高峰,14 d时下降。③转染Egr-1 decoyODNs治疗后,在各个时间点内膜增厚程度减轻,Egr-1和ICAM-1表达减少,与假手术组比较差异有统计学意义P<0.01)。结论 Egr-1 decoy ODNs可能是通过特异性抑制Egr-1的表达,进而抑制ICAM-1的表达,从而减轻血管损伤后内膜增生。
【Objectives】 To observe the effects of the local transfection of decoy oligodeoxynucleotides targeting Egr-1（early growth response factor-1）（Egr-1 decoy ODN） on neointimal formation and intercellular cell adhesion molecule-1（ICAM-1） expression after artery balloon,and explore its possible mechanism of inhibiting neointimal formation.【Methods】 Ninety-six male Wistar rats were randomly divided into four groups： sham-group,injury-only-group,scrambled decoy ODNs（SCR） group and EGR-1 decoy oligodeoxynucleotides（decoy ODNs） group.Six rats of each group 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 ICAM-1 were detected by RT-PCR and western blotting.【Results】 The thickening of intima began on the day after injury,and became more significant on the 14th and 21st day. The level of Egr-1mRNA and protein began to increase on the 3rd day and peaked on the 21st day,ICAM1 mRNA and protein peaked on the 7th day,declined on the 14th day.Compared with the SCR and Injuryonly-groups,NH was decreased significantly in Egr-1 decoy ODNs-treated rats（P 0.05）.Both mRNA and protein expression of Egr-1 and ICAM-1 in the Egr-1 decoy ODNs group were decreased at each time point（P 0.05）.【Conclusion】 Egr-1 decoy ODNs can inhibit intimal hyperplasia after artery injury by decreasing the expression of Egr-1 and ICAM-1.
出处
《中国现代医学杂志》
CAS
CSCD
北大核心
2013年第5期39-45,共7页
China Journal of Modern Medicine
