外源性野生型P16^(ink4a)基因在兔损伤动脉壁的表达  

Effect of the overexpression of exogenous P16^(ink4a) gene on the formation of restenosis after arterial injury

作　　者：张亚文[1] 张国元[1] 黄长晖[2] 邹祝英[2] 

机构地区：[1]第二军医大学附属长征医院心内科,上海200003 [2]第二军医大学分子遗传学开放实验室,上海200433

出　　处：《中国病理生理杂志》2000年第11期1159-1162,2002,共5页Chinese Journal of Pathophysiology

基　　金：第二军医大学遗传学开放实验室资助

摘　　要：目的 :研究转染外源性野生型P16 ink4a基因逆转录病毒重组质粒对兔颈总动脉壁损伤后再狭窄形成的抑制作用。方法 :构建野生型P16 ink4a基因的复制缺陷型逆转录病毒重组质粒 ,经包装细胞包装后取得高滴度病毒液 ,并以此病毒转染损伤后即刻的兔颈总动脉。应用膜杂交和原位杂交技术检测损伤动脉壁的外源性P16 ink4a基因表达 ,并通过病理学等方法观察动脉内膜增生情况及管腔狭窄程度。结果 :逆转录病毒重组质粒可有效地将外源基因P16 ink4a转入兔体内动脉壁并在其中表达。P16 ink4a基因转染组动物的损伤动脉壁内膜平滑肌细胞增生 (11 80± 3 5 4vs 2 5 2 0± 5 12 ,P <0 0 5 )和管腔狭窄程度 (5 0 2 %± 9 6 0 %vs 82 2 %±12 83% ,P <0 0 5 )均显著低于对照组。结论 :体内转染外源性野生型抑癌基因P16AIM: The present study is to investigate the inhibitory effect of the transfer of replication-defective retroviral recombinant plasmid encoding a wild-type P16 ink4a gene on the formation of restenosis after rabbit carotid arterial injury in vivo.METHODS:A replication-defective retroviral recombinant plasmid encoding wild-type gene P16 ink4a was constructed and the packaged high titer virus stock was obtained. It was transferred into the rabbit carotid arterial wall immediately after injury. The P16 ink4a mRNA expression in the arteries was examined by Northern blot and in situ hybridization. The effect of overexpression of the P16 ink4a gene on arterial intima hyperplasia was determined by pathophysiological method. RESULTS: The exogenous P16 ink4a could be effectively transferred into injured arterial wall by retroviral recombinant plasmid and the gene products could inhibit smooth muscle cells proliferation (11.80±3.54 vs 25.20±5.12,P<0.05) and arterial stenosis (50.2%±9.60% vs 82.2%±12.83%,P<0.05)。CONCLUSION: Transfer of the exogenous wide-type tumor-inhibiting gene P16 ink4a could prevent arterial restenosis in vivo, indicating a gene therapy approach for vascular proliferation disorders associated with arterial injury.

关 键 词：颈总动脉壁损伤 P16^INK4A基因 基因表达 

分 类 号：R543.402[医药卫生—心血管疾病]