腺相关病毒介导重组血管抑素联合雷公藤红素对大鼠颅内C6胶质瘤的抗血管生成作用  

Anti-angiogenesis effect of adeno-associated virus-mediated recombinant angiostatin combined with celastrol on intracranial C6 glioma in rats

作　　者：王冠[1] 周洁[1] 冯珂珂[2] 田麒[1] 

机构地区：[1]天津中医药大学第二附属医院神经外科,天津300151 [2]天津市环湖医院神经外科,天津300060

出　　处：《肿瘤》2011年第10期875-880,共6页Tumor

基　　金：国家自然科学基金资助项目(编号:30600633)

摘　　要：目的:腺相关病毒(adeno-associated virus,AAV)介导的重组血管抑素(angiostatin,AS)联合应用雷公藤红素(celastrol)治疗大鼠颅内C6胶质瘤,观察其对肿瘤体积、新生血管密度及肿瘤细胞凋亡的影响,探讨抗血管生成重组基因联合雷公藤红素对胶质瘤治疗的前景。方法:建立颅内原位荷C6脑胶质瘤大鼠模型,7d后随机分为4组,分别给予0.9%氯化钠溶液(作为对照)、AAV-AS、雷公藤红素及两者联合用药。每隔7d行头部强化MRI检查,计算肿瘤体积。于22d后处死动物,检测AS蛋白表达、血管密度及肿瘤细胞凋亡情况。结果:联合治疗组及AAV-AS治疗组均检测到AS蛋白表达,证实基因转导成功。联合治疗组第22天时肿瘤体积、血管密度和凋亡指数均与对照组、雷公藤红素组及AAV-AS治疗组相比差异有统计学意义(P<0.05),联合治疗可以抑制肿瘤生长,降低新生血管密度,促进肿瘤细胞凋亡。结论:基因治疗联合雷公藤红素可通过抑制胶质瘤血管生成而抑制肿瘤生长;两者联合应用具有协同作用,可弥补两者单独应用的不足之处。Objective： To examine the effects of therapeutic alliance of adeno-associated virus- mediated recombinant angiostatin （AAV-AS） combined with celastrol on tumor growth, microvessel density and apoptosis of intracranial glioma in rats, and to give a prospective of this therapeutic alliance. Methods： A rat intracranial C6 glioma model was established, and then the rats （n=40） were randomly assigned into four groups after 7 days, which were saline control group, AAV-AS group, celastrol group and therapeutic alliance group. The tumor growth was examined by magnetic resonance imaging （MRI） every 7 days, and the volume of tumor was calculated. The rats were killed after 22 days, and the expression of AS protein, the microvessel density and the apoptosis of tumor cells were detected. Results： The expression of AS protein was detectable in AAV-AS group and the therapeutic alliance group, which confirmed the achievement of genetic transduction. The tumor volume, microvessel density and apoptosis index were significantly different in the therapeutic alliance group compared with the other three groups （P〈O.05）. The therapeutic alliance of AAV-AS combined with celastrol could inhibit the tumor growth, reduce the microvessel density of tumor, and enhance the apoptosis. Conclusion： Gene therapy of AAV-AS combined with celastrol can inhibit glioma growth by inhibiting tumor vasculogenesis. This therapeutic alliance exerts a synergic effect and compensates the shortage of single drug.

关 键 词：神经胶质瘤 血管抑制素类 基因疗法 药物疗法 细胞凋亡 雷公藤红素 

分 类 号：R739.41[医药卫生—肿瘤]