内皮型一氧化氮合酶基因转染对血管损伤后新生内膜增生的影响

Effects of endothelial nitric oxide synthase gene transfection on neointima hyperplasia after vascular injury

背景:一氧化氮能够抑制血管平滑肌细胞的迁移和增殖,而一氧化氮合酶是其合成的关键酶,有关一氧化氮合酶基因体内转染对平滑肌细胞及动脉粥样硬化血管损伤后内膜增生影响少有报道。目的:观察内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)基因体内局部转染对动脉粥样硬化大鼠血管损伤后新生内膜增生的抑制作用。方法:建立动脉粥样硬化Wistar大鼠颈动脉球囊损伤模型,建模后随机分成空白对照组、AdCMV-lacz对照组和AdCMV-eNOS组,分别将PBS,AdCMV-lacz和AdCMV-eNOS体内转染至以上3组大鼠的损伤血管壁。转染2周后培养并鉴定损伤局部平滑肌细胞,并用RT-PCR法检测各组损伤及转染后血管平滑肌细胞eNOS mRNA的表达,同时观察转染后不同时期新生内膜增生的影响。结果与结论:AdCMV-eNOS组的颈总动脉血管平滑肌细胞可表达eNOS mRNA。3组大鼠转染后1和3个月,AdCMV-eNOS组内膜/中膜面积比值低于空白对照组和AdCMV-lacz对照组(P<0.01)。结果显示,eNOS基因体内转染损伤后血管可以抑制血管新生内膜增生,减少再狭窄发生率。

BACKGROUND：Nitric oxide （NO） can inhibit the proliferation and migration of vascular smooth muscle cells （VSMCs） and endothelial nitric oxide synthase （eNOS） is an important factor of the synthesis of NO.However,the effects of eNOS gene transfection on neointimal hyperplasia after balloon injury in atherosclerosis rats remain unclear.OBJECTIVE：To study the inhibition effects of eNOS gene transfection on neointimal hyperplasia after balloon injury in atherosclerosis rats.METHODS：The common carotid catheter injury model in atherosclerosis rats was established.All animals were divided into blank control,AdCMV-lacz and AdCMV-eNOS groups.Immediately after angioplasty,AdCMV-eNOS or AdCMV-lacZ or PBS was transfected into the injured segment of the common carotid artery for local therapy.Two weeks later,the transfected vascular were obtained to detect expression of eNOS mRNA in cultured smooth muscle cells.And then intimal-media ratio and neointimal hyperplasia were measured at different time points.RESULTS AND CONCLUSION：The transfected common carotid arteries were confirmed the mRNA expression of eNOS gene in cultured smooth muscle cells.At 1 and 3 months after transfection,the intimal-media ratio was significantly reduced in AdCMV-eNOS transfected group than PBS group or AdCMV-lacZ transfected group （P0.01）.eNOS gene transfection might strongly inhibit neointima hyperplasia after balloon injury in atherosclerosis rats and reduce arterial restenosis.