应用c-myc反义寡核苷酸防治自体静脉移植物内膜增生的实验研究

Reduction of intimal hyperplasia in autogenous vein graft by antisense c-myc oligodeoxynucleotide

目的：研究局部应用反义寡核苷酸ｃ－ｍ ｙｃ对自体静脉移植物内膜增生的防治作用，为反义技术防治血管内膜增生的早期临床应用提供实验依据。方法：３０ 只新西兰兔颈外静脉间置于同侧颈总动脉后随机分成对照组、蛋白胶组、正义组、反义组及错配组，以医用生物蛋白胶分别溶解反义、正义及错配的ｃ－ｍ ｙｃ基因片段（３３０ μｇ）后直接涂于静脉移植物外膜。术后２８ｄ 取材制片，显微镜进行形态观察，并用计算机图像分析系统测量和计算内膜厚度、中膜厚度及二者之比值，内膜面积、中膜面积及二者之比值，以ｑ 检验行统计学分析。结果：反义组增生内膜厚度较对照组降低３６．７７％ ，内膜面积降低４８．２２％ ，对照组、蛋白胶组、正义组及错配组间内膜厚度及内膜面积均无明显差异（Ｐ＞ ０．０５）；各组间中膜厚度及中膜面积均无明显差异（Ｐ＞ ０．０５）。结论：医用生物蛋白胶携载反义寡核苷酸ｃ－ｍ ｙｃ局部用于静脉移植物外膜能显著防治其内膜增生，有效防止管腔狭窄。

Objective: To evaluate the inhibitory effect of antisense phosphorothioate c myc oligodeoxynucleotide on intimal hyperplasia in autogenous vein graft.Methods:Thirty male New Zealand rabbits with external jugular veins interposed between ipsilateral common carotid arteries were randomly and equally divided into 5 groups.The antisense,sense and mismatch c myc oligodeoxynucleotide of 330 μg were dissolved in Fibrin glue and applied to the adventitia of vein graft. Twenty eight days after intervention,the animals were sacrificed and defined segments of vein grafts were sectioned and observed under microscope,the image was digitalized by computer video analysis system, the intimal thickness and area,medial thickness and area and their ratios were calculated and analyzed statistically among groups.Results:The intimal thickness and area in antisense group decreased to 63.23% and 51.78% of controls,respestively, while the intimal thickness and intimal area had no significant deviation among control,Fibrin glue,sense and mismatch groups.The medial thickness and area among each group were compared without significant deviation.Conclusion:Antisense c myc oligodeoxynucleotide can significantly suppress the intimal hyperplasia in vein graft by locally delivered with Fibrin glue.The investigation provides the basis for the early clinical trials assessing the therapeutic potential of antisense c myc approach for the prevention of restenosis after vein grafting.