反义c-myc寡脱氧核苷酸联合^(188)Re放射治疗对家兔髂总动脉损伤后内膜增生的影响

The Inhibitory Effect of locally delivered c-myc Antisense Oligonucleotides combined ^(188)Re Radian Therapy on Intimal Hyperplasia in Rabbit Common Iliac Arteria after Injury with a Ballon Catherer

目的观察反义c-myc寡脱氧核苷酸联合188Re放射治疗对家兔髂总动脉损伤后内膜增生的影响,探讨反义c-myc寡脱氧核苷酸(ODN)联合188Re防治再狭窄的潜在作用。方法通过球囊导管对家兔髂总动脉损伤后的血管照射后,将反义c-mycODN通过pluronicgel缓释系统和Lipofectin转染导入系统,将其作用于损伤血管的外膜,3周后对所取的血管节段进行组织切片和苏木精—伊红染色,在显微镜下进行形态观察和采用图像分析系统进行图像分析,计算出内膜/中膜(I/M)面积之比和I/M厚度之比,并进行统计学分析。结果通过形态观察和I/M面积和I/M厚度之比,发现单纯反义c-mycODN和188Re放射治疗,以及两者联合均能明显抑制内膜增生,且后者比前两者抑制更明显。结论反义c-mycODN联合188Re放射治疗能显著抑制新生内膜的形成。

Objective To investigate the effect to c-myc antiense oligonucleotides （ASODNs） combining ^188Re targeting c-myc proto oncogene on the neointimal thickening in rabbit common iliac arteria injured by the porous balloon catheter to explore the therapeutic potential of c-myc ASODNs for prevention of restenosis. Methods After the radian therapy with the 2.5mm balloon catheter filled with ^188Re,c-myc ASODNs was applied to the adventitia of injured common iliac arteria in rabbit introduced by pluronic gel releasing system lipofectin delivery system. Three weeks atter intervention, the animals were killed and defined segments of arteries were sectioned and the histological sections were stained with HE staining. The cross-section of the artery was examined microscopically and the image was digitalized by image analysis system. The intima/media （I/M） area and I/M thickness ratios were calculated and analyzed statistically among groups. Results The intimal hyperplasia in c-myc ASODNs-treated, ^188Re-treated and the combining therapy rabbits were inhibited significantly, and the inhibited effect of combining group was more significant than others, demonstrated by microscopiacally and I/M area and thickness ratios, as compared with sense c-myc ODN and other groups. Conclusion The c-myc ASODNs combining ^188Re significantly suppressed the intimal hyperplasia in injured rabbit common iliac arteria in sequence-specific fashion.