eNOS基因转染预防静脉移植血管再狭窄

Recombinant endothelial nitric oxide synthase gene transfer inhibits vein grafts neointima formation

目的 应用含牛内皮型一氧化氮合成酶 (e NOS)基因重组腺病毒 (Ad5 CMVNOS )转染静脉移植血管 ,观察 e NOS基因预防静脉移植血管再狭窄的作用。 方法 将 2 1只杂种犬分为 3组 ,手术对照组、Ad5 CMVL ac- Z(含大肠杆菌 β半乳糖苷酶基因重组腺病毒 )对照组和 Ad5 CMVNOS 干预组。在犬颈静脉、颈动脉旁路血管移植术中分别应用 Ad5 CMVNOS 病毒液或 Ad5 CMVL ac- Z病毒液常温浸泡法感染静脉移植血管 30分钟 ,术后 2 8天病理切片观测移植血管新内膜增生状况。 结果 与正常犬颈外静脉相比 ,手术对照组、Ad5 CMVL ac- Z对照组和Ad5 CMVNOS 干预组颈外静脉移植血管内膜 /中膜比较均有不同程度增加 (P<0 .0 5 ) ,但 Ad5 CMVNOS 组内膜 /中膜比显著低于另外 2个对照组 (P<0 .0 5 ) ,新内膜增生明显减轻。 结论 Ad5 CMVNOS 感染静脉旁路移植血管对预防再狭窄有一定作用。

Objective To evaluate nitric oxide augmentation in venous tissue by adenoviral-mediated gene transfer of endothelial nitric oxide synthase (Ad5CMVNOSⅢ) to reduce vein grafts restenosis. Methods Twenty-one canine were divided into three groups: operation control group, Ad5CMVLac-Z control group, and Ad5CMVNOSⅢ group. During operation of canine jugular vein into carotid artery interposition grafting, harvested canine jugular vein segments were exposed for 30min at 37℃ to either recombinant replication deficient adenovirus encoding eNOS(Ad5CMVNOSⅢ, 4.08× 10 10 pfu/ml), or control recombinant replication deficient adenovirus encoding E. coli β-galactosidase (Ad5CMVLac-Z, 2×10 10 pfu/ml). Quantitative histological studies of the vein segments were performed 28 days after operation. Results The average intimal-to-medial (I/M) ratio was calculated for each group one month after bypass operation. Compared to I/M ratio of normal canine jugular vein, the I/M ratio of operation control group veins, Ad5CMVLac-Z control group veins and Ad5CMVNOSⅢ group veins all increased significantly ( P <0.05). However, the I/M ratio of Ad5CMVNOSⅢ group vein grafts increased significantly less ( P <0.05). Conclusion Ad5CMVNOSⅢ gene therapy may reduce intimal hyperplasia.