转VEGF基因对血管损伤后修复过程中基质金属蛋白酶表达的影响

VEGF gene transfer modulates MMPs expression after vascular balloon injury

目的 :观察局部转染血管内皮生长因子 (VEGF)基因对血管球囊拉伤后修复过程中基质金属蛋白酶(MMPs)及其组织抑制因子 (TIMPs)表达的影响。方法 :90只新西兰大白兔随机分为 3组 ,Ⅰ组单纯拉伤右髂动脉 ;Ⅱ组拉伤后局部转染真核表达质粒AdtrackCMV ;Ⅲ组拉伤后局部转染pAdtrackCMV -VEGF1 65 ;每组按实验终点随机分为 5个亚组 ,术前一周开始给予高脂饮食至实验终点。取拉伤段髂动脉用于总RNA提取、组织病理和免疫组化检测。结果 :3组动物血脂水平保持在正常的 5 - 1 0倍 ,组间血管损伤程度评分相似 (P >0 .0 5)。Ⅰ、Ⅱ组整个观察过程中均可检测到MMP2、TIMP1 ,2持续表达 ;而转VEGF基因组术后 3d时可检测到MMP1 ,2 ,9、TIMP1 ,2表达 ,1周时达到高峰 ,8周时无表达。结论 :血管损伤后修复过程中存在MMPs和TIMPs表达失衡 ,致使基质堆积 ,并发生病理性重塑 ,而局部转染VEGF基因选择性改变局部MMPs表达 。

AIM: To investigate the effect of VEGF gene transfer on matrix metalloproteinases(MMPs) and tissue inhibitor of metalloproteinases(TIMPs) expression after vascular balloon injury. METHODS: 90 New Zealand white rabbits were divided into 3 groups randomly: group Ⅰ(balloon injury group), groupⅡ (pAdtrackCMV group) and group Ⅲ(pAdtrackCMV-VEGF165 group). Hypercholesterol diet was given for 7 days before experiment and continued to receive until the animals were killed. Each group were divided into five subgroups according to the sacrifice time. Blood samples and iliac arteries were harvested for further analysis. RESULTS: In group Ⅰ and Ⅱ, MMP2 and TIMP1,2 expressions were detected during the whole process ,while in group III ,MMP1,2,9 and TIMP1,2 could be detected from 3 days after gene transfer and reached the highest level at 1 week and could not be detected at 8 week. CONCLUSIONS: Imbalance expression of MMPs and TIMPs occurred after vascular injury and this may be the reason of pathological remodeling. Local phAdtrackCMV-VEGF165 transfer could specifically change the expression of MMPs and facilitate the positive remodeling process after vascular injury.