肿瘤坏死因子-α基因治疗联合放疗抗大鼠胶质瘤C6细胞作用的实验研究  

Combined Ad-rhTNF-α Gene Therapy and Radiotherapy——Study in a C6/ Subcutaneous Malignant Glioma Model of Wistar Rat

作　　者：王贵怀[1] 刘慧风[1] 李储忠[1] 孙梅珍[1] 候利军 

机构地区：[1]北京天坛医院神经外科 [2]北京中海阳光科技有限公司,北京100050

出　　处：《中国神经肿瘤杂志》2006年第2期118-124,共7页Chinese Journal of Neuro-Oncology

摘　　要：背景与目的:恶性胶质瘤预后差,有必要探索新方法提高疗效。本研究用Ad-rhTNF-α基因治疗联合放疗治疗大鼠皮下C6胶质瘤,评估其疗效和安全性。方法:基因工程技术构建Ad-rhTNF-α后,建立大鼠皮下胶质瘤模型,联合治疗组瘤内注射Ad-rhTNF-α,24h后行X线加速器放疗,各对照组作相应处理。放疗5天后处死所有大鼠进行形态学研究。结果:联合治疗组肿瘤体积最小,有丝分裂细胞数量最少,坏死区域最广,凋亡小体最为多见。联合治疗组外周血Th/Ts比值降低(P<0.05),NK细胞数量增多(P<0.05),体内免疫机制上调,效应细胞数量增多,免疫活性增强。各组体重与全血细胞分析的各项指标很接近。结论:Ad-rhTNF-α基因治疗放射联合治疗抗大鼠C6胶质瘤肿瘤作用明显优于单纯放疗和基因治疗,并且在目前剂量下是安全的。BACKGROUND ＆ OBJECTIVE： Experimental studies are fundamental for new treatment of gliomas. This study was to evaluate both the efficacy and safety of the combined Ad-rhTNF-α gene therapy and radiotherapy in a subcutaneous malignant glioma model of Wistar rat. METHODS： C6 glioma cells were implanted subcutaneously into the area of the fight leg of rat （day 0）. After the glioma model was successfully developed, the rats with glioma were divided into 5 groups： Ad-rhTNF/radiation group, Ad-rhT- NF-α group, radiation group, NS group, no treatment group. And there was another control group of normal rats without glioma. On day 5, Ad-rhTNF-α was injected into the tumor. X-ray irradiation （10 Gy, single fraction） was performed 24 hours thereafter and, on day 10, all the animals from each group were executed for assay procedures. RESULTS： Histological evaluation revealsed that the Ad-rhTNF/radiation group has developed the smallest tumors with the lowest number of tumor cells undergoing mitosis. While apoptotic bodies were common and tumor necrosis area was abundant. Flow cytometry of blood lymphocytes showed the highest number of Ts cells and NK cells in the Ad-rhTNF/radiation group. MTS indicatesd that the activity of lymphocytes in blood and spleen of the Ad-rhTNF/radiation group has been enhanced significantly than that of the radiation group （P〈 0.05）. Blood cells analysis and the body weight of the rats were similar among all groups. CONCLUSION： The combination of the two modalities for malignant glioma treatment is safe and effective.

关 键 词：Ad—rhTNF—α基因治疗 放射治疗 大鼠C6胶质瘤模型 

分 类 号：R739.41[医药卫生—肿瘤]