缺氧诱导因子-1α和同源盒基因表达对血管细胞信息传递连接生成的影响

摘要

Objective To explore the study between the expressions the HIF-la and gax gene mRNA on the intimal hyperplasia and the vascular cell communication and signal transduction in venous autograft (VEC-VSMC). Methods 20 Wistar rats weighing 200 -300 g were randomly divided into control and experimental groups (n = 14). Autogenesis vein graft model was established by transplanting the right external jugular vein into right common carotid artery in 20 rats. The transplanted vein in the experimental group was immersed in solution with recombinant adeno-associated virus (rAAV) HIF-la for 15 minutes before anastomosis and coated using glue gel in which rAAA gax added just after anastomosis, while the control ones were immersed only in the physiological salt solution in which recombinant adeno-associ-atedvirus solution without HIF-la gene added, nothing to be coated except for glue gel only. The vein grafts were taken at 14 days after oper ation. TUNEL, electric microscope were used to detect the vascular cell communication and signal transduction and the expressions of HIF-1 a mRNA, gax mRNA, phenotypic switch of vascular smooth muscle cells ( VSMCs) , vascular endothelium cells ( VECs) , PCNA ( prolifer ation cell nuclear antigen) , and apoptosis on VSMC in vein graft. Results In the experimental group, there was remarkable increase of expressions on HIF-la, gax gene mRNA and TUNEL, and significantly decrease of degree of VSMC proliferation in autovenous graft in rat. The novoendotheliasis and VEC-VSMC junction in vein grafts were remodeling at 14 days after operation in the experimental group. Conclusions HIF-la and gax gene can significantly promote a remodeling of VEC-VSMC communication and signal transduction. It may be one of signal paths on the inhibitory of vascular restenosis.%目的 探讨缺氧诱导基因(HIF)-1α和同源盒基因(gax)表达水平对移植静脉血管内皮细胞(VEC)与血管平滑肌细胞(vSMC)之间信息传递连接(VEC-VSMC细胞连接)的影响及其分子机制.方法 20只大鼠随机分为实验组与对照组,于术后14 d取出移植静脉,分别采用RT-PCR、免疫蛋白印迹、免疫组织化学及电镜,分析HIF-1α和gax基因及其蛋白的表达；观察VEC、VSMC表型以及VEC-VSM细胞信息传递连接.结果 实验组与对照组比较,HIF-1α和gax mRNA与蛋白表达明显增加(P均＜0.05)；内皮修复显著、内膜增生被显著抑制；可见较多的VEC-VSMC细胞信息传递连接结构体.结论 HIF-1α和gax基因过表达可显著促进VEC-VSMC细胞连接的生成,VEC-VSMC细胞连接信息连接可能是抑制血管再狭窄主要途径之一.