中文摘要：

目的探讨贝伐单抗（Avastin）对人胶质母细胞瘤移植瘤瘤体和血管生成的影响。方法免疫缺陷的RAG-KO小鼠,接种稳定表达荧光素酶的人胶质母细胞瘤U373-luc细胞7 d后将合格的载瘤小鼠随机分成4组（每组6只）：对照组（给予PBS）,低剂量贝伐单抗组,常规剂量贝伐单抗组,高剂量贝伐单抗组。每隔3 d记录各组小鼠重量,荧光成像系统每周2次测量颅内肿瘤体积随贝伐单抗治疗进程的改变。给药3周后,处死小鼠取材免疫组化检测肿瘤组织的CD31表达,计算微血管密度。小鼠处死前一天抽血测定血清血管内皮生长因子（VEGF）水平。结果与对照组相比,瘤体和血浆内VEGF水平显著下降,常规剂量和高剂量治疗组前两周肿瘤体积明显减少,血管密度减低,但3周起肿瘤体积反弹。常规剂量与高剂量治疗组之间各项指标未见明显差异。结论贝伐单抗对人胶质母细胞移植瘤瘤体和血管生成早期有明显抑制作用,可缩小肿瘤体积,减少血管密度,但随着治疗的延长,肿瘤生长反弹。接受高剂量和常规剂量贝伐单抗注射的载瘤小鼠均无明显不良反应。

英文摘要：

Objective To explore the anti-proliferation and angiogenesis effect of bevacizumab（ Avastin） on human glioblastomamultiforme（ GBM）. Methods U373 cells stably transfected with a luciferase expression plasmid（ U373-Luc） were injected into the brains of RAG-KO mice with a Hamilton syringe under anesthesia. Seven days after inoculation,the mice were randomly divided into4 groups（ 6 mice per group）. Treatment was initiated after 7 days of tumor cell implantation,according to the following regimens：（ 1） Control groups receive appropriate vehicles（ PBS）;（ 2） bevacizumab;（ 3） bevacizumab;（ 4） bevacizumab. Tumor growth was assessed twice a week by bioluminescence imagingusing a Xenogen In Vivo Imaging system. We weighed the mice every 3days and recorded the time until they reached their humane end-points. Three weeks after the treatment,solid tumors from sacrificed mice were OCT-embedded. Expression of CD31 were detected by immunohistochemical method. The microvessel density（ MVD） were assessed under microscope. ELISA method was used to measure the expression level of the vascular endothelial growth factor（ VEGF）. Results The expression VEGF and MVD was significantly decreased in both 10 mg / kg and 20 mg / kg treated group when compared to control group and 2. 5mg / kg treated group. The growth of tumor in 10 mg / kg and20 mg / kg treated group remarkably reduced during the initial 2weeks,however,it rebound to quick growth from the third week. Conclusions These findings suggest that bevacizumab can notably inhibited tumor cell proliferation and tumor angiogenesis,but the effects declined with the time oftreatment. Adverse drug reaction was not found in high dose treated group.