IS导管血管壁内局部导入c-myc反义寡核苷酸预防PTCA术后再狭窄的实验研究

Local delivery of c-myc antisense oligodeoxynucleotide on vessel wall to prevent restenosis following PTCA

目的 探讨IS导管局部导入c myc反义寡核苷酸及c myc反义寡核苷酸对血管平滑肌细胞的抑制作用。方法 2 1只家兔 ,对照组 6只 ,反义寡核苷酸治疗组 15只。用IS导管导入c myc反义寡核苷酸 (1mg)于球囊损伤的髂动脉后 ,动脉血管造影。病理切片 ,图象分析测定新生内膜、中膜、面积和厚度 ,c myc蛋白免疫组化染色。 结果 动脉造影对照组 5 0 %～ 80 %局限狭窄 ,给药组 10 %～ 30 %局限狭窄。光镜观察结果显示 :血管内膜增生面积给药组为 (4.0 4± 1.0 2 )× 10 5μm2 ,对照组为 (7.6 6± 3.7)× 10 5μm ,(P <0 .0 5 ) ;对照组c myc免疫组织化学染色阳性 ,给药组血管c myc免疫组织化学染色显示弱阳性或阴性。结论 IS导管可在体局部导入反义寡核苷酸于动脉损伤靶点 ;c myc反义寡核苷酸可抑制SMCs迁移。

Objective To investigate the feasibility of local endoluminal delivery of c-myc oligodeoxynucleotide (ODN) to the site of arterial denudation by using Infusa Sleeve(IS) catheter and to determine the biological importance of these effects. Methods IS catheter was introduced into the right side of the iliac artery of 21 rabbits after angioplasty of iliac artery. The animals were randomly divided into the control group (n=6) receiving saline injection and the treatment group receiving c-myc protein detected by using a mouse monoclonal antibody to c-myc. Morphometric analysis was carried out on day 40 after transcatheter c-myc antisense oligomer administration. Results Maximal neointimal area was reduced from 766±3.7(×10 5?μm 2) in the control group (n=6) to 4.04±1.02 (×10 5μm 2) in the antisense treatment group (n=6,P<0.05). These changes in vascular remodeling following denuding injury resulted in an increase in residual lumen from 20%-50% in the control group to 70%-90% in the antisense treatment group; c-myc protein expression was virtually undetectable at baseline in locally ODNs-delivered arteries and detectable in control denuded arteries. Conclusion 1. Single IS transcatheter administration allows endoluminal delivery of ODNs to the site of arterial injury. 2 c-myc antisense oligomer may reduce the formation of neointima in denuded arteries, implying a therapeutic potential of this approach.