^(103)Pd放射性核素支架抑制损伤血管平滑肌细胞增殖的实验研究

Experiment Study on the Proliferation-inhibiting Effect of 103Pd Radioative Injured Vascular Smooth Muscle Cells

[目的]采用兔腹主动脉损伤致再狭窄的动物模型,探讨钯-103(103Pd)放射性核素支架对损伤血管中膜平滑肌细胞增殖的影响。[方法]选用雄性新西兰兔50只,随机分为普通支架组及核素支架组,设正常对照。分别于术后3、7、14、28及56 d取材,进行病理形态学、透射电镜、免疫组化(增殖细胞核抗原PCNA、细胞周期素蛋白Cy-clin E)及原位杂交(C-myc mRNA)实验观察。[结果]①光镜下发现,核素支架组管腔狭窄程度明显低于普通支架组,术后第56天最显著(P<0.01);②透射电镜显示,术后3~28 d,核素支架组中膜血管平滑肌细胞增殖明显低于普通支架组,7d时达峰,为13.78％±0.64％vs19.53％±0.44％(P<0.01);③免疫组化显示,术后3~28 d核素支架组PCNA及Cyclin E表达均低于普通支架组,7 d为表达高峰,PCNA为16.35％±0.79％vs24.36±0.55％,Cy-clin E为14.78％±1.07％ vs 22.65％±1.00％(P<0.01)。④对c-myc mRNA进行原位杂交显示,术后3~28 d核素支架组的表达明显低于普通支架组,7 d达峰值,为17.48％±0.53％ vs 25.34％±0.87％(P<0.01);⑤C-mycmRNA与PCNA相关性分析提示二者呈明显正相关(P<0.01)。[结论]103Pd放射性核素支架通过抑制损伤血管中膜平滑肌细胞的增殖,降低再狭窄的程度,从而减少再狭窄的发生率。

[Objective] By establishing restenosis animal model of rabbits' abdominal arteries, to evaluate the proliferation-inhibiting effect of 103Pd radioactive stent on injured media vascular smooth muscle cells. [Methods] Fifty male New Zealand rabbits were randomized into stent group and 103Pd stent group. Control group was set up. The materials were harvested on day 3, 7, 14, 28 and 56 after operation and the following investigation were carried out, including pathomorphology, transmission electron microscopy (TEM), immunohistochemistry and in situ hybridization studies. [ Results ] ①The severity of the stenosis in 103Pd stent group was less severe than that of stent group. It was most obvious on 56th day ( P < 0. 01). ② TEM analysis showed that the vascular smooth muscle cells' proliferation of 103Pd stent group was much lower than that of stent group from day 3 to day 28. The peak day was on 7th day, 13.78% ±0.64% vs 19.53% ±0.44% (P< 0. 01). ③The expression of PCNA and Cyclin E of 103Pd stent group was lower than that of stent group from day 3 to day 28. It was more obvious on 7th day. PCNA was 16. 35% ±0. 79% vs 24. 36% ±0. 55%. Cyclin E was 14. 78% ± 1. 07% vs 22. 65% ±1. 00% ( P < 0. 01). ④ In situ hybridization showed that the expression of C - myc mRNA of 103Pd stent group was much lower than that of stent group. The lowest expression was on 3th day, 17. 48%± 0. 53% vs 25. 34% ±0. 87% ( P < 0. 01). ⑤ Linear correlation analysis showed that there was significant positive correlation between the expression of C-myc mRNA and PCNA ( P < 0. 01). [Conclusion ]103Pd radioactive stent inhibites the proliferation of injured media vascular smooth muscle cells. It relieves the severity of restenosis and decreases the occurence of restenosis.