【作者】 包大士；

【导师】 惠国桢； 郭礼和；

【作者基本信息】 苏州大学 ， 神经外科， 2001， 博士

【摘要】 目的：构建重组缺陷型腺病毒血管抑素基因（angiostatin）载体，进行血管抑制基因治疗脑胶质瘤的体内及体外的实验研究。方法：RT-PCR法克隆血管抑素基因，同源重组共转染293细胞构建携带血管抑素基因的腺病毒载体，体外检测血管抑素的重组缺陷型腺病毒载体对内皮细胞增殖的抑制作用。建立大鼠皮下及脑内C6胶质瘤模型，给予体内基因治疗，观察及评价治疗脑胶质瘤的效果。结果：克隆得到约1.2Kb的血管抑素cDNA。构建携带血管抑素基因重组腺病毒载体AdhCMV-AGS，体外试验表明，重组载体可以强烈抑制内皮细胞的增殖。体内试验表明重组载体可以在体内表达血管抑素，并且有效抑制皮下胶质瘤的生长，使脑内荷C6胶质瘤大鼠长期存活。结论：以重组腺病毒为载体的血管抑素基因治疗脑胶质瘤效果显著，将是一种基因治疗肿瘤的新策略。更多还原

【Abstract】 Objective To study the therapy for C6 glioma with the recombinant adenovirus containing angiostatin eDNA (AdhCMV- AGS). Methods Angiostatin gene was cloned into vector pAdCMV-AGHpA to make pAdhCMV-AGS. Recombinant adenovirus was constructed in 293 cells contransfected with pAdCMV(AGS) and pJM17. Detected the effect of AdhCMV-AGS on proliferation of endothelial cells(ECV3O4) in vitro. Made a model of rat C6 brain glioma, then observed tumors size and survival of tumor-bearing rats treated with AdhCMV-AGS. Results AdhCMV-AGS could inhibited the proliferation of ECV3O4 cells significantly, but not C6 cells. The size of tumors injected with AdhCMV-AGS decreased. Some of it even disappeared, while the size of control (injected with saline solution) was larger significantly. the survival time of groups were beyond 90 days (with AdhCMV-AGS), 16.8 ±3.3 days(with Ad-null), 16.7±2.5 days(with saline) (p<0.001). Conclusion AdhCMV-AGS could inhibit the proliferation of endothelial cells and the angiogenesis by which it suppressed C6 glioma. Ours results suggest that antiangiogenesis gene therapy will be a promising way of treating tumors that have abundant capillary.更多还原