HSV-tk基因对实验性血管成形术后再狭窄的抑制作用

Inhibitory Effect of the Herpes Simplex Virus Thymidine Kinase Gene on Experimental Restenosis after Balloon Angioplasty

为探讨转染单纯疱疹病毒胸苷激酶（ＨＳＶｔｋ）基因联合ｇａｎｃｉｃｌｏｖｉｒ（ＧＣＶ）治疗方案用于治疗冠状动脉成形术后再狭窄的可行性，构建了携带ＨＳＶｔｋ基因的复制缺陷型逆转录病毒，利用该病毒将ＨＳＶｔｋ基因转染至体外培养的血管平滑肌细胞（ＶＳＭＣ）和大鼠腹主动脉再狭窄模型的损伤动脉中，并均给予ＧＣＶ，分别观察上述处理对ＶＳＭＣ的增殖和新生内膜的形成是否有抑制作用。结果：该方案使培养的ＶＳＭＣ增殖受抑制，抑制程度对ＧＣＶ有剂量依赖关系；既往在恶性肿瘤中发现的旁观者效应，在培养的ＶＳＭＣ中也存在。同时，该方案使大鼠腹主动脉再狭窄模型的新生内膜面积减少。但单纯转染ＨＳＶｔｋ基因或单纯应用ＧＣＶ无论在体外还是在体内均无上述抑制作用。提示本基因治疗方案对人类冠脉成形术后再狭窄有治疗价值。

To investigate the feasibility of transduction with the herpes simplex virus thymidine kinase(HSVtk) gene combined with ganciclovir(GCV) treatment, a recently proposed gene therapy strategy for restenosis after balloon angioplasty of the coronary arteries, a replicationdefective retrovirus containing the HSVtk gene was constructed, and the inhibitory effect of the strategy on both vascular smooth muscle cell(VSMC) proliferation and neointima formation was observed in vitro and in a rat aorta model of restenosis, respectively. The result showed that the strategy inhibited cultured VSMCs proliferation, which was dosedependent on GCV. The bystander effect, which was previously demonstrated in malignancies, proved existent in cultured VSMC as well. In the rat aorta model of restenosis, the strategy was shown to reduce injuryinduced neointimal expansion. In contrast,neither transduction with the HSVtk gene nor GCV treatment independently produced the antiproliferative effect both in vitro and in vi sis; gene therapy The Second Affiliated Hospital, Hebei Medical Universityvo. The data suggests the potential utility of this gene therapy strategy for human restenosis after the balloon angioplasty.