摘要
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％。
Objective:Tissue plasminogen activator (t PA) gene therapy may provide a novel therapeutic strategy in preventing thrombotic diseases . The goal of this study was to detect the expression duration of the t PA gene transferred into the arterial wall in vivo and whether the gene therapy was able to prevent restenosis following angioplasty. Methods:18 canines , including 6 in the control group and 12 in the gene therapy group with 3 subgroups of 30,60,90 days were studied. Retroviral vectors containing t PA cDNA were directly delivered into 10 coronary and 12 femoral arterial walls of the 12 canines while 6 coronaries of 6 canines in the control group were perfused with TE buffer, via porous perfusion balloon catheter when canine restenotic models were established. The existence of t PA cDNA and the expression of active t PA products were tested by in situ hybridization, mRNA dot blot and immunohistochemistry at different time of 30, 60 and 90 days. Results :Our results showed the presence of t PA gene with active expression product in the gene therapy group and the percent area stenosis decreased 22.2% in the gene therapy group at 90 days compared with the control one. Conclusion: The t PA gene therapy is able to decrease the neointimal proliferation in the canine restenotic model, and prevent the restenosis after angioplasty to some degree.
出处
《中国循环杂志》
CSCD
1996年第7期406-410,共5页
Chinese Circulation Journal
