重组腺相关病毒介导HIF-1α基因对移植静脉再内皮化的影响

Effects of HIF-1α mRNA overexpression transferred by recombinant adeno-associated virus on novoendotheliasis of vascular endothelial cell in the venous autografts

目的 探讨缺氧诱导因子 1α(HIF 1α)过表达对大鼠移植静脉再内皮化的影响。方法 56只大鼠,随机分为实验组和对照组,均行自体右颈内静脉移植至同侧颈总动脉手术,实验组移植静脉经HIF 1α重组腺病毒工作液预处理。分别于术后7 d或14 d切取移植静脉和血清。检测和观察组织标本中HIF 1αmRNA、血管内皮细胞生长因子(VEGF)、E 选择素(E selectin)的表达及内皮细胞再内皮化的情况。结果 实验组与对照组比较,HIF 1αmRNA表达增强(P<0 01);HIF 1α和VEGF蛋白表达明显增加(P<0 01);血清E selectin含量明显降低(P<0 05)。内皮细胞增殖和肌内皮连接重建显著。结论 移植静脉重塑早期HIF 1α过表达可促进受损血管内皮细胞(VEC)结构和功能的重建,加速再内皮化进程。

Objective To explore the effects of overexpression of hypoxia inducible factor 1α (HIF 1α) mRNA on vascular endothelial growth factor (VEGF) and novoendotheliasis in venous autografts Methods Wistar rats were randomly divided into two groups with 28 rats in each group A rat experimental model of autogenous vein graft was established by transplanting the right external jugular vein into between the interrupted right common carotid artery The transplanted vein in the experimental group was first immersed into a solution containing recombinant adeno associated virus (rAAV) HIF 1α for 45 minutes Vein grafts and blood simples were taken at 7 or 14 days after transplantation RT PCR, ELISA, immunohistochemistry were used to detected HIF 1α mRNA and VEGF expression Results HIF 1α mRNA and VEGF protein remarkably increased in experimental group, and serum level of E selectin significantly decraesed at day 14 The novoendotheliasis and myo endothelium junction in vein grafts were remodeled at day 14 in the experimental group Conclusion Re establishment of the structure and function of the autograft vein graft endothelium was accelerated by overexpressed HIF 1α mRNA