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目的 构建表达鼠白介素 12 (IL 12 )基因的重组单纯疱疹病毒 (HSV IL12 ) ,并测试对大鼠C6脑胶质瘤的实验治疗。方法 将IL 12的 p35和p4 0的两个亚单位基因分别插入单纯疱疹病毒的ICP34.5区 ,构建HSV IL12。结果 缓激肽开放血脑屏障的同时灌注HSV IL12显著地延长了动物的生存时间 ,有 4 0 %的动物生存期超过了 10个月。离体脾脏细胞CTL分析没有检测出T淋巴细胞溶解活性 ,而从肿瘤内收集的T淋巴细胞却有强烈的杀伤活性。结论 缓激肽开放血脑屏障的同时灌注HSV IL12可能是一个很有潜力的治疗脑胶质瘤的手段。
Objective To construct recombinant herpes simplex virus (HSV IL12) expressing murine interleukin 12 (IL 12) gene and to test the experimental treatment of rat C6 glioma. Methods Two subunit genes of p35 and p40 of IL12 were inserted into the herpes simplex virus (ICP34.5) region to construct HSV IL12. Results Bradykinin perfusion with HSV IL12 while opening the blood-brain barrier significantly prolongs the survival time of animals, and 40% of animals have been alive for more than 10 months. CTL analysis of isolated spleen cells did not detect T lympholytic activity, whereas T lymphocytes collected from tumors showed strong cytotoxic activity. Conclusions Bradykinin may be a potential therapeutic agent for gliomas by opening blood-brain barrier with simultaneous infusion of HSV IL12.