纳米磁粒靶向基因治疗动脉闭塞性疾病的实验研究  

An experimental study of gene therapy targeted by magnetic nanosphere for occlusive vascular disease

作　　者：张铁民[1] 许军[1] 姜洪池[1] 赵金朋[1] 魏兰兰[2] 庄敏[2] 陈秀林 谷鸿喜[2] 

机构地区：[1]哈尔滨医科大学第一临床医学院普外科,150001 [2]哈尔滨医科大学微生物教研室 [3]黑龙江鹤岗矿务局总院兴安医院外科

出　　处：《中华普通外科杂志》2004年第11期699-701,共3页Chinese Journal of General Surgery

基　　金：2003年黑龙江省自然科学基金资助项目(D0322);2002年哈尔滨市科技攻关计划资助项目(2002AA9CS15122)

摘　　要：目的创立一种新的基因治疗闭塞性血管病的方法。方法采用共沉淀法合成了纳米级磁粒,以逆转录聚合酶链式反应法(RTPCR)克隆人血管内皮生长因子基因并构建高拷贝的真核表达质粒,应用乳化复合技术合成磁粒基因复合微球。中国大耳白兔20只,制造后肢动脉血管闭塞模型。10d后经对侧股动脉注入磁粒基因复合微球,患侧肢体外加磁场。治疗后30d处死动物,分别取肌肉及内脏组织做病理切片。结果血管造影显示治疗组第40天有新生血管形成,并向远断端生长,使得肢体远端血供得以恢复。对照组亦可见血管新生,但数量明显少于治疗组(P<005)。对照组缺血肢体大腿中部肌肉组织(内收肌和半膜肌)微血管密度为(125±23)个mm2,治疗组为(298±27)个mm2,P<001;微血管数和肌纤维数两者比率对照组为042±004,治疗组为083±003,P<001。结论纳米磁粒靶向VEGF基因治疗实验性血管闭塞性病变疗效显著,安全可靠。Objective To evaluate a new gene therapy for the treatment of experimental occlusive arterial disease Methods Magnetic nanospheres were produced, VEGF gene was cloned for subsequent construction of eukaryotic expression plasmid The magnetic gelatin microspheres used in targeted gene therapy were prepared by emulsion crosslinking method The microspheres were injected intrafemorally in rabbits through contralateral femoral artery, and the ischemic limb was placed in a magnetic field Angiography was performed on day 10 and day 30 respectively The capillary density and the capillary to muscle fiber ratio were determined histochemically Results Compared to the controls there was significant collateral artery development in VEGF transfected group The capillary density and the capillary to muscle fiber ratio were significantly higher for the VEGF transfected group than for the control group. The capillary density of control was (125±23)/mm 2, and in VEGF group was (298±27)/mm 2, P <0 01 The capillary to muscle fiber ratio in control was 0 42±0 04 and in VEGF group was 0 83± 0 03, P <0 01 Conclusion Gene therapy targeted by nanospheres is an easy, efficient and safe method for the treatment of experimental occlusive vascular disease

关 键 词：治疗组 靶向 对照组 肢体 基因治疗 动脉闭塞性疾病 血管内皮生长因子 实验研究 新生血管形成 治疗后 

分 类 号：R654.3[医药卫生—外科学]