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目的：组织型纤溶酶原激活剂（ｔ－ＰＡ）基因治疗，为防治血栓性疾病提供了一个可能全新的方法与前景。探索ｔ－ＰＡ基因转移至犬血管壁后基因表达持续的时限以及预防血管成行术后再狭窄的价值。方法：１８条家犬，其中对照组６条，另１２条在形成再狭窄模型时随机分为３０天、６０天和９０天３个观察亚组，每组４条犬，并用多孔球囊输注导管将携带ｔ－ＰＡ基因的逆转录病毒载体直接高压注入冠状动脉及股动脉壁。结果：经过３０天、６０天和９０天不同时间的观察，发现在脱氧核糖核酸（ＤＮＡ）水平（原位杂交、ＤＮＡ印迹）、转录水平［（信使核糖核酸（ｍＲＮＡ）点杂交］及产物水平（免疫组化）等方面均证实ｔ－ＰＡ基因的存在和活性产物表达，而且发现再狭窄组３个月时基因治疗组比对照组的百分狭窄面积小２２．２％。结论：ｔ－ＰＡ基因治疗有一定的预防血管成形术后再狭窄的作用
OBJECTIVE: Tissue-type plasminogen activator (t-PA) gene therapy provides a promising new method and prospect for the prevention and treatment of thrombotic diseases. To explore the duration of gene expression after t-PA gene transfer to the canine wall and the value of preventing restenosis after angioplasty. Methods: 18 dogs, including 6 control subjects, and the other 12 rabbits were randomly divided into three subgroups: 30 days, 60 days and 90 days, with 4 dogs in each group. The catheter is injected directly into the coronary and femoral artery walls with a retroviral vector carrying the t-PA gene. Results: After 30 days, 60 days and 90 days of observation, it was found that there was no significant difference in DNA level (in situ hybridization, Southern blotting), transcription level [(messenger RNA hybridization) and product level (Immunohistochemistry) confirmed the presence of t-PA gene and the expression of active product, and found that restenosis group 3 months when compared with the gene therapy group, the percentage of stenosis was 22.2% smaller.Conclusion: t- PA gene therapy has a certain effect of preventing restenosis after angioplasty