放射性核素支架预防血管再狭窄的基础及动物实验研究

Mechanism and animal model study of low-dose radioactive stents for prevention of restenosis

目的 探讨放射性核素对培养平滑肌细胞增殖及凋亡的作用及其机制 ,观察放射性核素支架预防再狭窄的可行性及有效性。方法 将培养平滑肌细胞分为188Re照射组与非照射组 ,应用细胞及分子生物学技术 ,研究了放射性核素188Re对离体平滑肌细胞增殖、凋亡、次黄嘌呤鸟嘌呤磷酸核糖转移酶 (HPRT)基因突变的作用 ;将兔损伤髂动脉内随机放置放射性支架与非放射性支架 ,观察了放射性核素支架对动物血管再狭窄模型的预防作用。结果 与非照射组比较 ,188Reβ辐射 (放射比活度为 0 74、1 4 8、2 2 2、2 96、3 70GBq/L)能够明显抑制平滑肌细胞的增殖 ,抑制细胞增殖率 (1 4 8～3 70GBg/L) [(10 0 0 %vs 34 1% ,t =2 5 0 0 ,P <0 0 5 ) ,(10 0 0 %vs 2 7 7% ,t=2 74 4 ,P <0 0 5 ) ,(10 0 0 %vs 2 1 8% ,t=2 972 ,P <0 0 5 ) ,(10 0 0 %vs 18 1% ,t=3 12 1,P <0 0 5 ) ],阻滞细胞进入DNA合成期 { [(43 5 6± 2 32 ) %vs (2 3 80± 2 5 7) % ,t =11 4 16 ,P <0 0 0 1],[(43 5 6± 2 32 ) %vs(11 82± 2 5 1) % ,t =18 5 6 6 ,P <0 0 0 1],[(43 5 6± 2 32 ) %vs (6 0 4± 1 2 0 ) % ,t =2 8 734,P <0 0 0 1],[(43 5 6± 2 32 ) %vs (3 30± 0 5 2 ) % ,t=33 892 ,P <0 0 0 1],[(43 5 6±

Objective To explore the effects and the mechanism of radionuclide on smooth muscle cells proliferation and apoptosis, and to investigate the effects of radioactive stents on prevention of restenosis Methods The effects and mechanism of radionuclide on the proliferation, apoptosis, and mutation of HPRT gene exon 7/8 in cultured smooth muscle cells were studied by cellular and molecular technique, and the prevention effects of radioactive stents on restenosis were investigated in animal model Results The proliferation of smooth muscle cells cultured in vitro could be inhibited markedly by β particle radiation from radionuclide 188 Re, proliferation inhibition rate: [(100 0% vs 34 1%, t =2 500, P <0 05), (100 0% vs 27 7%, t =2 744, P <0 05), (100 0% vs 21 8%, t =2 972, P <0 05), (100 0% vs 18 1%, t =3 121, P <0 05)]; DNA synthesis inhibition rate: {[(43 56±2 32)% vs (23 80±2 57)%, t =11 416, P <0 001], [(43 56±2 32)% vs (11 82±2 51)%, t =18 566, P <0 001], [(43 56±2 32)% vs (6 04±1 20)%, t =28 734, P <0 001], [(43 56±2 32)% vs (3 30±0 52)%, t =33 892, P <0 001], [(43 56±2 32)% vs (1 49±0 87)%, t =33 991, P <0 001]} The apoptosis of smooth muscle cells couldn′t be affected significantly by low dose radiation But there was an increase of apoptosis rate only in group 3 70 GBq/L [(2 89±0 56)% vs (17 21±2 56)%, t =9 477, P <0 001] There was a positive relationship between the radiation dose and the mutation of HPRT gene and exon 7/8 ( r =0 993, P <0 001; r =0 947, P <0 05) Radioactive stents could decrease neointimal area [(1 01±0 37) mm 2 vs (0 60±0 29) mm 2, t =2 466, P <0 05], and percent area of stenosis [(16 84±6 61)% vs (10 05±4 27)%, t =2 448, P <0 05] compared with non radioactive stents in animal restenosis model Conclusion Endovascular radiotherapy in low dose and low dose rate was an ideal therapy selection for prevention of restenosis, which could inhibit cell proliferation significantly, but didn′t ruin the vessel structure Radioactive stents could inhibit the restenosis in the animal model, and it is safe and feasible for prevention of restenosis