早期反应生长因子1特异的脱氧核酶对大鼠动脉损伤后血管内皮功能的保护及超微结构的影响
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辽宁省科学技术计划项目基金(2002225002-2)


Effects of DNA Enzyme Targeting Egr-1 on Endothelial Function and Ultrastructure of Rat Carotid Artery after Bolloon Injury
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    摘要:

    目的探讨早期反应生长因子1特异的脱氧核酶对大鼠实验性颈总动脉损伤后内皮功能及超微结构的影响。方法Wistar大鼠96只,随机分为假手术组、对照组1(MgCl2)、对照组2(FuGENE6)和ED5治疗组,每组24只。行左颈总动脉内膜剥脱术后,ED5治疗组经球囊导管将ED5 500μg、注入损伤的血管节段内,作用20 min。对照组1注入200μL的1 mmol/L MgCl2液,对照组2注入含FuGENE6 30μL的1 mmol/L MgCl2液200μL。分别于第3、7、14和第21天各处死动物6只,处死前心脏取血检测一氧化氮、一氧化氮合酶、内皮素,同时光镜及透射电镜观察血管形态学变化。结果ED5治疗组一氧化氮和一氧化氮合酶含量均较两对照组增高,第14天最明显,此时一氧化氮与两对照组相比分别为57.1±1.9μmol/L比38.7±1.9μmol/L和57.1±1.9μmol/L比38.3±1.9μmol/L,差异有显著性统计学意义(p<0.05);一氧化氮合酶分别为11.1±0.4μmol/L比8.1±0.4μmol/L和11.1±0.4μmol/L比8.0±0.4μmol/L,差异有显著性统计学意义(p<0.05)。而内皮素浓度较两对照组有所降低,以第14天最显著,分别为111.2±7.2 pg/L比136.6±7.2 pg/L和111.2±7.2 pg/L比135.5±7.2 pg/L,差异有显著性统计学意义(p<0.05)。光镜观察发现ED5治疗组新生内膜厚度较两对照组明显减轻,以第21天最明显(64.0±4.2μm比81.1±4.9μm和64.0±4.2μm比80.0±3.9μm,p<0.01)。透射电镜观察发现对照组血管新生内膜的平滑肌细胞呈“合成型”改变,而治疗组新生内膜的血管平滑肌细胞呈“收缩型”改变。结论早期反应生长因1特异的脱氧核酶可改善动脉球囊损伤后的血管内皮功能,抑制血管平滑肌细胞的表型改变,从而减轻内膜增生程度。

    Abstract:

    Aim To investigate the effects of 10-23DNA enzyme(ED5) on endothelial function and ultrastructure change of Carotid Artery after injured artery in rats. Methods Ninety-six rats were randomly divided into sham-group,control-group 1,control-group 2 and ED5-group(n=24).The models of endothelial denudation of rats were made by using balloon catheter,FITC-ED5 was delivered to the artery wall of ED5-group in a total of 200 μL solution.Rats of control-group1 were given 200 μL 1 mmol/L MgCl2.Rats of control-group2 were given FuGENE6 Reagent.Six rats were killed at the 3rd,7th,14th,21th day after balloon injury.The serum level of nitric oxide and nitric oxide synthase and endothelin were detected.At the same time,to observe pathological change of injured arteries by optical microscope and electron microscope. Results The serum level of nitric oxide and nitric oxide synthase in ED5-group were higher than those in 2 control groups,increased significantly on the 14th day(nitric oxide: 57.1±1.9 μmol/L vs 38.7±1.9 μmol/L and 57.1±1.9 μmol/L vs 38.3±1.9 μmol/L,p<0.05;nitric oxide synthase: 11.1±0.4 μmol/L vs 8.1±0.4 μmol/L and 11.1±0.4 μmol/L vs 8.0±0.4 μmol/L,p<0.05);but endothelin in ED5-group was lower than that in 2 control groups,obviously different on the 14th day(111.2±7.2 pg/L vs 136.6±7.2 pg/L and 111.2±7.2 pg/L vs 135.5±7.2 pg/L,p<0.05).Compared with ED5-group,the neointimal thickness in 2 control groups increased significantly on the 21th day after balloon injury(64.0±4.2 μm vs 81.1±4.9 μm and 64.0±4.2 μm vs 79.5±3.9 μm, p<0.01).The vascular smooth muscle cell of neointima in 2 control groups may be contractile type,but vascular smooth muscle cell of neointima in ED5-group may be synthetic type. Conclusion The ED5 can improve the endothelial function after artery injury and inhibit the phenotype transform of vascular smooth muscle cells,and reduce the degree of neointimal hyperplasia.

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滕雅轩,刘闺男,周敬.早期反应生长因子1特异的脱氧核酶对大鼠动脉损伤后血管内皮功能的保护及超微结构的影响[J].中国动脉硬化杂志,2005,13(6):709~712.

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  • 收稿日期:2004-12-22
  • 最后修改日期:2005-11-19
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