Effect of Local Transfection of Survivin Antisense Oligodeoxyribonucleotides on Intimal Hyperplasia in Vein Graft_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

YANG Jun , HU Xinhua , LIU Chengwei , ZHANG Zhishen , ZHANG Qiang.

Department of Vascular Surgery, The First Affiliated Hospital, China Medical University, Shenyang 110001, China;

Corresponding author：

Keywords：

Intimal hyperplasia; Survivin; Oligodeoxyribonucleotide

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Objective　To investigate the effect of survivin antisense oligodeoxyribonucleotides (survivin ASODNs) on intimal hyperplasia (IH) in vein graft in rats. Methods　 Autogenous vein graft models were established in 60 Wistar rats by transplanting the interior jugular vein to the common jugular artery using microsurgical technique. The rats were divided into 5 groups according to random digits table, including survivin ASODNs 50 μg group and 200 μg group, scramble ODNs 200 μg group (ODNs group）, Lipofectin+pluronic group and control group. Vein graft samples were collected on 7 d and 14 d after transplantation, respectively. The degrees of hyperplasia were determined and then compared by histomorphology between different groups. The expression of survivin mRNA was measured by RT-PCR and immunohistochemistry. The relevant protein products were detected by Western blot and immunohistochemistry was also used to detect the expression of PCNA. Apoptosis of VSMC was measured by TUNEL.Results　Day 7 and 14 were the days that intimal hyperplasied most in control group, ODNs group and Lipofectin+pluronic group, there was no significant difference among these groups yet (P gt;0.05). The IH could be suppressed by locally transfecting 50 μg of survivin ASODNs (P＜0.05), and it showed a better inhibiting effect in 200 μg of survivin ASODNs group (P＜0.05). The expression of survivin mRNA increased significantly in control group. The expressions of both survivin and PCNA in VSMC significantly decreased in survivin ASODNs group (P＜0.05), whereas the positive cells of TUNEL increased significantly (P＜0.05). Conclusion　Transfection of survivin ASODNs may inhibit the IH after vein graft through suppressing the hyperplasia and stimulating the apoptosis of VSMC, and inhibiting the expression of survivin.

Citation： YANG Jun,HU Xinhua,LIU Chengwei,ZHANG Zhishen,ZHANG Qiang.. Effect of Local Transfection of Survivin Antisense Oligodeoxyribonucleotides on Intimal Hyperplasia in Vein Graft. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2006, 13(6): 647-652. doi: Copy

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2. 　冯　勇，段志泉，胡海地，等. 移植静脉平滑肌细胞凋亡及相关基因表达与增殖关系的动态研究 [J]. 中华医学杂志， 1999; 79(1)∶15.
3. 　Sambrook J, Fritsch EF, Maniatis T. 克隆化基因所表达蛋白质的检测与分析 [A]. 见：金冬雁，黎孟枫译. 分子克隆实验指南 [M]. 第2版. 北京：科学出版社, 1992∶852～898.
4. 　Yang D, Welm A, Bishop JM. Cell division and cell survival in the absence of survivin [J]. Proc Natl Acad Sci USA， 2004; 101(42)∶15100.
5. 　Thury A, van Langenhove G, Carlier SG, et al. High shear stress after successful balloon angioplasty is associated with restenosis and target lesion revascularization [J]. Am Heart J， 2002; 144(1)∶136.
6. 　胡新华，张　强，孙达欣，等. 核转录因子κB及其抑制基因在自体移植静脉中的表达 [J]. 中华医学杂志, 2002; 82(22)∶1546.
7. 　胡新华，杨　军，张　强，等. 核转录因子κB decoy寡核苷酸对移植静脉内膜增生的影响 [J]. 中华外科杂志， 2003; 41(9)∶684.
8. 　Bennett MR, Schwartz SM. Antisense therapy for angioplasty restenosis. Some critical considerations [J]. Circulation， 1995; 92(7)∶1981.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of Local Transfection of Survivin Antisense Oligodeoxyribonucleotides on Intimal Hyperplasia in Vein Graft

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