联合转染反义c-myc寡核苷酸和组织纤溶酶原激活物基因预防损伤后动脉内膜增生的研究

目的观察血管局部联合转染c-myc反义寡核苷酸(AODN)和组织纤溶酶原激活物(tPA)基因对损伤后动脉内膜增生的影响。方法将同一只兔的左、右髂外动脉(各1·0cm)对换移植,移植血管分别用脂质体、c-myc-AODN和pBudCE4·1/tPA液浸泡,血管吻合口用上述3种液体浸泡过的缝线吻合。实验终点(术后3、7、14、28、56d)分为5个亚组,术后各实验终点取移植血管标本用于病理学检测、发色底物法检测tPA活性实验、3H-TdR掺入实验和免疫组织化学染色检测。结果术后各时间点联合转染组血管的内膜面积、管腔狭窄程度、3H-TdR掺入量和增值细胞核抗原(PCNA)阳性细胞数均显著低于对照组(P<0·01),而且亦明显低于c-myc-AODN和tPA单独转染组(P(0·05)。结论血管局部联合转染c-myc-AODN和tPA基因能有效抑制内膜增生,防止损伤血管狭窄。

Co-transfection of tPA gene and c-myc antisense oligodeoxynucleotides for the prevention of intimal hyperplasia of rabbit auto-transplantion artery

Objective To observe the effects of co-transfection of proto-oncogene c-myc antisense oligodeoxynucleotides(c-myc-AODN) and tissue-type plasminogen activator(tPA) gene on intimal hyperplasia of auto-transplantion artery in rabbit. Methods The left and right external iliac artery(length 1.0 cm) of rabbits were cross transplanted. The artery grafts and sutures were respectively soaked in Lipofection, c-myc-AODN, pBudCE4.1/tPA, c-myc-AODN and pBudCE4.1/tPA solution for 15 minutes. Each group were divided into five subgroups(n=5, in each subgroup) according to the sacrifice times(3, 7, 14, 28 and 56 d after operation). Specimens were harvested for pathology, chromogenic substrate test, 3H-TdR incorporation test and immunochemisty coloration study. Result The intimal area, stenosis ratio, 3H-TdR incorporation, PCNA positive cell in c-myc-AODN adding tPA co-transfection group were significantly lower than that of control group(P0.01), and that were lower than c-myc-AODN transfection group and tPA gene transfection group(P0.05). Conclusion Vascular local co-transfection of tPA gene and c-myc-AODN effectively inhibits the proliferation of vascular smooth muscle cell(VSMC) and hyperplasia of intima of the transplanted artery.