rhTNF联合环磷酰胺对胶质瘤的靶向作用  

Targeting effect of rhTNF combined with cyclophosphamide on glioma

作　　者：秦丽娟[1] 王健[1] 王海涛[2] 贾永森[3] 周洪霞[4] 王树华[5] 

机构地区：[1]河北联合大学基础医学院生理学教研室,河北唐山063000 [2]河北联合大学基础医学院组织学与胚胎学教研室,河北唐山063000 [3]河北联合大学中医学院,河北唐山063000 [4]河北联合大学基础医学院解剖学教研室,河北唐山063000 [5]河北联合大学基础医学院药理学教研室,河北唐山063000

出　　处：《吉林大学学报（医学版）》2013年第4期755-758,I0004,共5页Journal of Jilin University：Medicine Edition

基　　金：河北省卫生厅科学研究基金资助课题(20120144)

摘　　要：目的:探讨重组人肿瘤坏死因子(rhTNF)联合环磷酰胺(CTX)对胶质瘤的靶向作用,并阐明其作用机制。方法:构建C6胶质瘤大鼠模型,将大鼠分为rhTNF组(n=10)、CTX组(n=10)及rhTNF-Dex-CTX组(n=10)。免疫荧光法观察肿瘤坏死因子受体1(TNFR1)在胶质瘤组织中的表达;利用125I-rhTNF,通过放射配基结合受体分析法检测大鼠脑组织和胶质瘤组织中rhTNF水平;ELISA法检测大鼠脑组织和胶质瘤组织中CTX水平;观察rhTNF、CTX及rhTNF-Dex-CTX偶联物对胶质瘤大鼠生存时间的影响。结果:TNFR1在胶质瘤细胞中的表达明显高于肿瘤血管内皮细胞。rhTNF在胶质瘤组织中与TNFR1的结合量明显高于正常脑组织(P<0.01)。CTX组大鼠脑组织和胶质瘤组织中CTX水平均较低;与CTX组和大鼠正常脑组织比较,rhTNF-Dex-CTX组大鼠胶质瘤组织内CTX的水平明显升高(P<0.01)。与CTX组和rhTNF组比较,rhTNF-Dex-CTX组大鼠的生存时间明显延长(P<0.01)。结论:rhTNF-Dex-CTX可能是通过TNFR1增强CTX对胶质瘤的靶向作用。Objective To investigate the targeting effect of recombinant human tumor necrosis factor（rhTNF） combined with cyclophosphamide（CTX）on glioma and to clarify its mechanism.Methods C6glioma rat models were established and divided into rhTNF group（n=10）,CTX group（n=10）and rhTNF-Dex-CTX group（n=10）.The immunofluorescence method was used to observe tumor necrosis factor receptor 1（TNFR1）expression in glioma tissue;radioligand receptor binding analysis was performed to determine the rhTNF concentration in brain tissue and glioma tissue;ELISA assay was used to detect the CTX levels in brain tissue and glioma tissue;the influence of rhTNF,CTX and rhTNF-Dex-CTX in survival time of glioma rats was observed.Results The TNFR1expression in glioma cells was significantly higher than that in tumor vascular endothelial cells.The amount of rhTNF combined with TNFR1in glioma tissue was significantly higher than that in normal brain tissue（P0.01）.The CTX levels in the brain tissue and glioma tissue of the rats in CTX group were lower;compared with CTX group,the CTX level in glioma tissue of the rats in rhTNF-Dex-CTX group was significantly increased;compared with CTX and rhTNF groups,the survival time of the glioma rats in rhTNF-Dex-CTX group was significantly prolonged（P0.01）.Conclusion rhTNF-Dex-CTX may increase targeting effect of CTX on glioma by combining with TNFR1.

关 键 词：胶质瘤 重组人肿瘤坏死因子 环磷酰胺 rhTNF-Dex-CTX偶联物 

分 类 号：R739.41[医药卫生—肿瘤]