转血管内皮生长因子基因对血管损伤后重塑的影响及机制探讨  

The beneficial effect of phVEGF165 transfer on vascular remodelling after balloon injury and its possible mechanisms

作　　者：韦方[1] 耿庆山[1] 张斌[1] 冯建章[1] 林华欢[2] 蒋祖勋[1] 余细勇[3] 周钢[3] 

机构地区：[1]广东省心血管病研究所心内科 [2]广东省人民医院病理科 [3]广东省心血管病研究所分子药理室

出　　处：《中华病理学杂志》2002年第5期436-439,共4页Chinese Journal of Pathology

摘　　要：目的　观察局部转染pAdtrackCMV VEGF16 5对血管球囊拉伤后重塑的影响并探讨可能机制。方法　 90只新西兰大白兔随机分为 3组 ,Ⅰ组 (30只 )单纯拉伤腹主动脉和右髂动脉 ;Ⅱ组 (30只 )拉伤后局部转染真核表达质粒pAdtrackCMV ;Ⅲ组 (30只 )拉伤后局部转染pAdtrackCMV VEGF16 5 ;每组按实验终点 (术后 3d、1周、2周、4周和 8周 )随机分为 5个亚组 ,术前 1周开始给予高脂饮食 ,继以高脂饮食喂养至实验终点。取拉伤段腹主动脉用于总RNA提取 ,拉伤段髂动脉 4%甲醛原位灌注固定后用于组织病理和免疫组织化学检测。结果　 3组动物血脂水平保持在正常的 5～ 10倍 ,组间血管损伤程度评分相似 (P >0 0 5 )。术后 2周时 ,Ⅲ组血管内膜加中膜面积明显小于Ⅰ、Ⅱ组 [(0 5 0± 0 32 )mm2 比 (0 94± 0 34 )mm2 、(0 92± 0 43)mm2 ,P <0 0 5 ],4周时Ⅲ组血管外弹力板下围绕面积明显大于Ⅰ、Ⅱ组 [(1 89± 0 31)mm2 比 (1 40± 0 2 0 )mm2 、(1 36± 0 2 1)mm2 ,P <0 0 5 ],狭窄程度明显低于Ⅰ、Ⅱ组 [(11 1± 3 1)mm2 比 (5 4 2± 7 6 )mm2 、(5 7 4± 7 7)mm2 ,P <0 0 1];术后 3d时 ,Ⅲ组血管组织可检测到VEGF16 5、基质金属蛋白酶 (MMP) 1,2 ,9及其组织抑制因子 (TIMP) 1,2表达 ,2周时达高峰 。Objective To investigate the effect of phVEGF165 transfer on vascular remodelling after balloon injury and its possible mechanisms. Methods 90 New Zealand white rabbits were divided randomly into 3 groups: group Ⅰ(balloon injury group), groupⅡ (pAdtrackCMV group) and group Ⅲ(pAdtrackCMV-VEGF165 group). All animals were given hypercholesterol diet for 7 days before experiment and continued to receive hypercholesterol diet until being killed. Each group was further divided into five subgroups according to the sacrifice time (3 days, 1, 2, 4 and 8 weeks after transfection). Blood samples and arteries were harvested for further analysis. Results At the end of 2 weeks, areas of neointima plus media of group Ⅲ were smaller than those of group Ⅰ and Ⅱ (P<0.05). The areas under external elastic membrane were larger in group Ⅲ at 4 weeks and lumen stenosis rates were significantly lower than groupⅠ and Ⅱ (P<0.05 or 0.01). In group Ⅲ, VEGF165, metalloproteinases (MMPs) -1, -2, -9 and their tissue inhibitors (TIMPs) 1, 2 could be detected from 3 days after gene transfer and reached the highest level at 2 weeks time and could not be detected by 8 weeks time. In groupsⅠ and Ⅱ, MMP-2 and TIMP-1, -2 could be detected during the whole procedure and the value of TIMP1/MMP1 was significantly higher than in group Ⅲ (P<0.01). Conclusion Remodelling is the main reason for restenosis(RS) after vascular balloon injury. Local pAdtrackCMV-VEGF165 transfer can specifically change the expression of MMPs and facilitate the positive remodelling process, hence, inhibiting restenosis.

关 键 词：血管内皮生长因子 血管损伤 冠状动脉再狭窄 基质金属蛋白酶 VEGF 

分 类 号：R541.4[医药卫生—心血管疾病]