反义C-myc寡核苷酸抑制血管吻合口狭窄的实验研究

EXPERIMENTAL STUDY ON INHIBITION OF VASCULAR ANASTOMOTIC STENOSIS BY ANTISENSE C-myc OLIGODEOXYNUCLEOTIDE

为了探讨局部应用反义C myc寡核苷酸对血管吻合口狭窄的抑制作用 ,将 30只新西兰大白兔颈外静脉间置于同侧颈总动脉后随机分成对照组、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 myc基因片段 (330 μg)直接涂于血管吻合口外周。术后 2 8天取材制片 ,进行形态观察 ,并用计算机图像分析系统测量和计算内膜、中膜厚度及二者之比值 ,内膜、中膜面积及二者之比值。结果发现 ,反义组增生内膜厚度较对照组降低 39%、内膜面积降低 5 1% ,对照组、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 0 5 ) ;各组间中膜厚度及中膜面积均无明显差异 (P >0 0 5 )。提示医用生物蛋白胶携载反义C myc寡核苷酸局部用于血管吻合口外膜能显著抑制其内膜增生 。

In order to evaluate the inhibitory effect of antisense C myc oligodeoxynucleotide on vascular anastomotic stenosis, thirty New Zealand white rabbits with external jugular veins interposed between ipsilateral common carotid arteries were randomly and equally divided into five groups. The antisense?sense and mismatch C myc oligodeoxynucleotide of 330μg each were dissolved in fibrin glue and applied to the adventitia of vascular anastomosis. Twenty eight days after intervention, the animals were sacrificed and defined segments near anastomosis were sectioned and observed under light 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 the groups. The intimal thickness in antisense group was reduced 39% than that of control group, intimal area decreased 51%, while no significant deviation was found in the intimal thickness and intimal area among control, fibrin glue, sense and mismatch groups( P >0 05). No significant deviation was found in medial thickness and area among each group( P >0 05). The results suggest antisense C myc oligodeoxynucleotide significantly suppressed the intimal hyperplasia in anastomosis by local fibrin glue. The investigation provides the basis for the early clinical trials of antisense C myc for the prevention of restenosis after anastomosis.