涂层支架局部导入c-myc反义核酸防治再狭窄的实验研究

Study on Local delivery of c-myc Antisense Oligodeoxynucleotide by Gelatin Coated Platinium-Iridium Stent to Prevent Restenosis in A Normal Rabbit Carotid Artery

目的:探讨铂-铱合金明胶蛋白涂层支架局部导入c-m yc反义寡核苷酸的可行性及对新生内膜的抑制作用。方法:将携带c-m yc反义寡核苷酸的国产铂-铱合金明胶蛋白涂层支架置入兔颈动脉(n=16),在术后7、14、30、90 d处死动物行HE和W e igert染色,图像分析测量新生内膜厚度和面积,c-m yc蛋白免疫组化染色并与对照组(n=16)进行对比分析。结果:随观察时间延长两组新生内膜面积和平均新生内膜厚度呈持续增加趋势,且不同观察时间点给药组新生内膜面积和平均新生内膜厚度均显著小于对照组(P均<0.001)。c-m yc免疫组化染色给药组为弱阳性和阴性,对照组为阳性。14 d时透射电镜观察显示血管平滑肌细胞呈过渡型改变。结论:国产铂-铱合金明胶蛋白涂层支架可携带c-m yc反义寡核苷酸于兔颈动脉局部,并抑制新生内膜的形成,提示支架可作为局部给药防治再狭窄的工具。

Objective：To investigate the feasibility and effect of local delivery of c-myc antisense oligodeoxynucleotide （ASODN） by gelatin coated Platinium-Iridium stent to prevent restenosis in a normal rabbit carotid artery. Methods：Gelatin coated Platinium-Iridium stent were implanted in the right carotid arteries of 32 rabbits under vision. Animals were randomized to the control group and the treated group receiving c-myc ASODN （n= 16） respectively. 7,14,30, 90 days following the stenting procedure ,morphometry for caculation of neointimal area and mean neointimal thickness were performed. The expression of c-myc protein was detected by immunohistochemical methods. Results： 32 stents were successfully implanted into the right carotid arteries in 32 animals. Morphometric analysis showed that neointimal area and mean neointimal thickness siginificantly increased continuously up to 12 weeks after stent implantation,and at each time point,neointimal area and mean neointimal thickness were siginificantly smaller in the treatedgroup than control group （P 〈0. 001 ） respectively, c-myc protein expression was Weak positive or negtive in treated group and positive in control group. Conclusion：Gelatin coated Platinium-Iridium stent mediated local delivery of c-myc ASODN is feasibility,and it can inhibit neointimal hyperplasia to prevent restenosis in a normal rabbit carotid artery.