野生型p53基因转移预防血管成形术后再狭窄的实验研究

Study on preventing restenosis after angioplasty by transferring human wild type p53 gene

目的探讨逆转录病毒载体介导的人野生型ｐ５３基因转移对预防血管成形术后再狭窄的作用。方法构建野生型ｐ５３基因逆转录病毒载体，通过逆转录病毒载体介导，将野生型ｐ５３基因转导至大鼠球囊损伤的颈动脉再狭窄模型中，２１ｄ后观察其对新生内膜形成的影响，并检测ｐ５３蛋白表达水平。结果构建和包装了人野生型ｐ５３基因的重组逆转录病毒载体，并在体外细胞中表达；用逆转录病毒载体转导野生型ｐ５３基因至大鼠球囊损伤的颈动脉，免疫组化检测表明转导血管局部表达人野生型ｐ５３蛋白，且与对照组相比，损伤血管新生内膜／中层面积比降低了４４％。

Objective: Vascular smooth muscle cell (VSMC)proliferation after injury is important in the pathogenesis of restenosis after balloon angioplasty. In current study,we observed the effects of human wild type p53 gene transduction by retroviral vector on preventing restenosis following angioplasty.Methods: We constructed recombinant retroviral vector expressing human wild type p53. It was transfected into the SD rat carotid artery after carotid balloon injury and the restenosis model was estabished. We measured neotima/media area ratio and detected human wild type p53 protein expression in the local artery at day 21 after gene transfer.Results: We constructed and packaged recombinant retroviral vector expressing human p53 gene.Human wild type p53 gene was transfected into local carotid artery after the rat carotid balloon injury. Human wild type p53 protein expression was detected in local artery by immunohistochemistry. Neotima/media area ratio was significantly reduced (44%,P<0.01) compared with the control group.Conclusion: The results suggest a cytostatic gene therapy approach for restenosis after angioplasty.