反义单核细胞趋化蛋白-1基因抑制移植静脉内膜增殖的实验研究  

Antisense monocyte chemotactic protein-1 gene inhibits vein graft intimal hyperplasia in rabbits

作　　者：李拥军[1] 管珩[1] 刘昌伟[1] 王宗立[2] 

机构地区：[1]中国医学科学院中国协和医科大学北京协和医院血管外科,100730 [2]中国医学科学院基础研究所病理科

出　　处：《中华外科杂志》2001年第9期718-720,W004,共4页Chinese Journal of Surgery

摘　　要：目的　探讨反义单核细胞超化蛋白 1(MCP 1)转基因表达对移植静脉术后局部血管MCP 1mRNA表达、单核巨噬细胞浸润及与其相关的内膜增生的影响。　方法　建立 14只兔颈外静脉 颈总动脉移植模型 ,并随机分为基因治疗组、载体对照组和空白对照组。应用阳离子脂质体介导 ,将反义MCP 1基因通过局部定位转染的方法转染至移植静脉段。RNA斑点杂交 ,检测反义基因转染、表达情况 ;病理形态学观察移植血管新生内膜增生以及血管壁中单核巨噬细胞粘附、浸润的情况。结果　RNA斑点杂交提示 :基因治疗组中有反义MCP 1基因表达。移植静脉自身MCP 1mRNA的表达受到明显抑制 (降低 38% ,P <0 0 5 )。相应的单核巨噬细胞在移植静脉中的粘附、浸润明显减少(减少 34% ,P <0 0 5 )。内膜增生程度显著减轻 (减轻 49% ,P <0 0 5 )。　结论　反义MCP 1局部移植静脉内转基因表达 ,可抑制移植静脉自身MCP 1的表达 ,抑制单核巨噬细胞的浸润 。Objective To identify the effect of in vivo local expression of recombine antisense MCP 1 gene on the development of vein graft neointima formation. Methods Jugular vein to artery bypass grafting was performed on 20 New Zealand white rabbits, of which 4 grafts were transferred with LNCX vectors, 6 grafts with antisense MCP 1 (200 μg) by cationic liposome, and 4 grafts as controls. Fourteen days after surgery grafts were harvested. The expression of antisense MCP 1 and its effect on MCP 1 in vein grafts were detected by dot blot. Grafts were processed for morphologic evaluation and immunohistochemistry analysis. Results Antisense MCP 1 was expressed in local gene delivery group, meanwhile MCP 1 expression in vein grafts was significantly inhibited (test group, 1 227±0 362; controls, 1 981±0 394, P <0 05). Monocytes/macrophages adherence and infiltration were prominently reduced (test group, 24 3%±2 7%; controls, 36 8%±2 8%, P <0 05), and intimal hyperplasia was markedly reduced [test group,(0 65±0 08) mm 2; controls, (1 27±0 15) mm 2, P <0 05]. Conclusion Local expression of antisense MCP 1 in vein graft significantly reduced intimal hyperplasia with inhibition of MCP 1 expression and prevention of monocytes/macrophages infiltration.

关 键 词：单核细胞趋化蛋白-1 静脉移植 基因疗法 反义基因 内膜增殖 

分 类 号：R654.4[医药卫生—外科学]