反义寡核苷酸防治血管吻合口内膜增生性再狭窄的机制探讨  

Appraisal of mechanism of preventing intimal hyperplasia on vascular anastomotic site by locally delivered antisense c-myc oligodeoxynucleotide

作　　者：曲乐丰[1] 景在平[1] 曹贵松[1] 仲剑平[1] 

机构地区：[1]第二军医大学长海医院血管外科,上海200433

出　　处：《上海医学》2002年第11期690-692,共3页Shanghai Medical Journal

基　　金：国家自然科学基金资助项目 (3 0 170 92 6)

摘　　要：目的　探讨医用生物蛋白胶携载c myc反义寡核苷酸防治血管吻合口内膜增生性再狭窄的机制。方法　将 8只新西兰大白兔颈外静脉间置于同侧颈总动脉后 ,随机分成实验组及对照组。对照组静脉间置后即缝合伤口 ;实验组将 30 0 μg反义c myc涂于2 .5ml医用生物蛋白胶中 ,并均匀涂于血管吻合口外周。术后 7d取材 ,提取组织总RNA ,进行RT PCR和NorthernBlot分析 ,图像扫描后进行计算机分析。结果　RT PCR显示实验组的c myc扩增产物量明显低于对照组 ,产物半定量分析提示两者差异有显著性 (P <0 .0 1) ;NorthernBlot图像扫描分析显示实验组的积分密度值 (2 .2 5± 0 .16 )明显低于对照组 (4.6 3± 0 .4 8) (P <0 .0 5 )。结论　反义c myc可通过碱基互补与其相应基因结合 ,封闭该基因的表达 ,使其促细胞增殖作用减弱 。Objective To elucidate the mechanism of attenuation of vascular intimal hyperplasia by antisense c myc oligodeoxynucleotide.Methods Eight male New Zealand white rabbits with external jugular veins interposed between ipsilateral common carotid arteries were randomly and equally divided into two groups. The antisense c myc oligomer of 330 μg was dissolved in fibrin gel and applied to the outer layer of vascular anastomotic site in the experimental group. Seven days later, the animals were sacrificed and the total RNA of the specimens was extracted. RT PCR and Northern blot analysis were carried out and the pictures were scanned and digitalized by computer.Results Both RT PCR and Northern blot analysis revealed a significant reduction of c myc expression in antisense c myc oligodeoxynucleotide treated tissues.Conclusion The results implied that the antisense c-myc oligomers can bind to the target mRNAs in accordance with the base complementary principle after entering the tissue cells. The target gene expression was inhibited and the cell proliferation was suppressed with eventual prevention of restemosis induced by intimal hyperplasia.

关 键 词：反义寡核苷酸 血管吻合口 血管内膜增生 动物实验 

分 类 号：R654.4[医药卫生—外科学]