C-sis反义寡脱氧核苷酸抑制兔主动脉平滑肌细胞增殖的时效关系

为观察局部处理C-sis反义寡脱氧核苷酸对平滑肌细胞增殖及新生内膜肥厚的抑制作用、球囊导管损伤60只新西兰白兔胸主动脉后。经导管局部处理每只兔1mg（2mL）C-sis反义或正义寡脱氧核苷酸或2mL生理盐水,于损伤后第3、7、14天和第28天，用免疫组织化学方法结合图象分析，评价损伤动脉内膜平滑肌细胞增殖及新生内膜改变。结果发现．C-sis反义寡脱氧核苷酸明显抑制内膜平滑肌细胞增殖，最高抑制作用出现于损伤后第3天；抑制百分率达69．8％，第7、14天和第28天的抑制率依次降低，分别为59％、51.9％和47.8％；而新生内膜面积的抑制百分率分别是48．9％、77．8％、72．6％和70．8％，与生理盐水处理组相比，平滑肌细胞数及新生内膜面积均有明显降低。研究结果表明，局部处理C-sis反义寡脱氧核苷酸，通过反义途径，可明显抑制球囊损伤主动脉内膜平滑肌细胞增殖，其抑制作用随时间而降低，同时，对新生内膜面积肥厚的最大抑制出现于第7天，随后降低，提示局部处理C-sis反义寡脱氧核苷醚，有可能降低再狭窄的发生。

Time-Effective Relation of Proliferation of Aortic Smooth Muscle Cells after Lo cal Delivery of C-sis Proto-oncogene Antisense Oligodeoxynucleotides in Injured Aorta of Rabbits

Aim To study the inhibitory effect of locally delivered c-sis proto-oncogene antisense oligodeoxynucleotide (ODN) on aortic smooth muscle cells (ASMC)proliferation and neointimal thickening. following balloon angioplasty in the rabbit aorta at differential time.Methods 60 male New Zealand, White Fabbits were treated with local delivery of c-sis antisense ODN,c-sis sense ODN, or 0. 9% salt solution via balloon catheter following aorta balloon injury, ASMC proliferation and area in neointima was assessed with immunohistochemistry and image analyzer at 3, 7, 14, 28 days after local delivery.Results ASMC proliferation in neointima were reduced 69. 8%. 59 %, 51. 9%, 47. 8% in c-sis antisense ODN-treated group compared to c-sis sense ODNtreated group at 3, 7, 14, 28 d following aortic injury respectively; and the inhibitory rate of neointimal hyperplasia was 48. 9%, 77. 8%, 72. 6%, 70. 8% at the same time respectively.Conclusion The locally deliveried C-sis antisense ODN inhibited ASMC proliferation and neointimal thickening following rabbit aortic injury, the inhibitory effect was the highest at 3 d and 7 d, then reduced slowly. and caused by antisense mechanism.