纳米磁粒靶向VEGF基因治疗闭塞性血管病的实验研究  

Experimental studies on occlusive vascular disease gene therapy targeted by magnetic nanosphere

作　　者：张铁民[1] 姜洪池[1] 许军[1] 潘尚哈[1] 

机构地区：[1]哈尔滨医科大学第一临床医学院普外科,黑龙江哈尔滨150001

出　　处：《哈尔滨医科大学学报》2003年第5期399-401,425,共4页Journal of Harbin Medical University

摘　　要：目的　创立一种新的基因治疗闭塞性血管病的方法 ,并验证其有效性及安全性。方法　应用乳化复合技术将纳米级磁粒与pcDNA3 VEGF1 6 5合成磁粒基因复合微球。选取中国大耳白兔 2 0只 ,随机分组建立血管闭塞模型。造模后 10d于对侧股动脉插管至髂动脉开口处注入磁粒基因复合微球 ,同时造模肢体外加磁场。分别于治疗前及治疗后 30d行血管内造影。治疗后 30d处死动物取标本 ,染色后显微镜下观察。结果　血管造影X线片可见治疗组造模后第 4 0天有大量新生血管形成 ,新生血管由髂内动脉向股浅动脉远断端方向生长 ,将二者连通 ,并且原有股浅动脉分支形成的侧支循环也大量开放。缺血肢体大腿中部肌肉组织在治疗后 30d微血管密度 :对照组为(12 5± 2 3) mm2 ,治疗组为 (2 98± 2 7) mm2 ,P <0 .0 1;微血管数和肌纤维数二者比率 :对照组为 0 .4 2± 0 .0 4 ,治疗组为0 .83± 0 .0 3,P <0 .0 1,均有显著差异。结论　纳米磁粒靶向VEGF基因治疗兔闭塞性血管病疗效显著 ,安全可靠。Objective To find a new way of gene therapy on occlusive vascula r disease,and to prove its efficiency and safety. Methods The magnetic gelatin microspheres used in targeted gene the rapy were prepared by emulsion-crosslinking method. The microspheres were injec t ed into ischemic limb in hare models through contralateral femoral artery. At th e same time the limb was in the control of magnetic field. Angiography was perfor med on day 0,day 10 and day 30,respectively. The capillary density and the capi l lary to muscle fiber ratio were determined histochemically in the resected sampl e. Pathological inspection was carried out on heart,spleen,liver,kidney,lung,bra in,retina,and so on. Results Marked progression of collateral artery development was obs erved in the VEGF-transfected group between days 0 and days 30. The assessment o f angiographic score verified the result. The capillary density and the capillar y to muscle fiber ratio were significantly higher in the VEGF-transfected group than in the control group. The capillary density:control,(125±23)/mm 2,VEGF , (298±27)/mm 2,P<0.01. The capillary to muscle fiber ratio:control,0.42± 0.04, VEGF,0.83±0.03,P<0.01. Abnormity in remote organs was not observed histolog ically. Conclusion Gene therapy targeted by nanospheres is an easy,efficien t and safe method for occlusive vascular disease,which significantly augmented the capillary formation and improved collateral artery development.

关 键 词：纳米磁粒 靶向 VEGF 基因治疗 闭塞性血管病 实验 安全性 血管内皮生长因子 

分 类 号：R543[医药卫生—心血管疾病] R394[医药卫生—内科学]