抗血管内皮生长因子抗体对异位子宫内膜鸡胚模型干预的研究  

The chick embryo chorioaUantioc membrane as a model for in vivo research on anti-angiogenesis in endometriosis

作　　者：王含必[1] 冷金花[1] 朱兰[1] 刘珠凤[1] 孙大为[1] 郎景和[1] 

机构地区：[1]中国医学科学院中国协和医科大学北京协和医院妇产科,100730

出　　处：《中华妇产科杂志》2007年第1期43-47,共5页Chinese Journal of Obstetrics and Gynecology

摘　　要：目的尝试构建子宫内膜异位种植的鸡胚模型,并利用此模型探讨抗血管内皮生长因子(VEGF)抗体在子宫内膜异位症(内异症)治疗中的作用机制。方法将人类的子宫内膜组织种植到鸡胚绒毛尿囊膜(CAM)上,采用分组对照研究,内异症对照组和非内异症对照组为分别种植内异症及非内异症患者的子宫内膜,以磷酸盐缓冲液作为药物对照;内异症实验组和非内异症实验组为分别种植内异症及非内异症患者的子宫内膜,使用抗 VEGF 抗体作用的鸡胚模型。末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸标记法(TUNEL)检测细胞凋亡、增殖细胞核抗原(PCNA)检测细胞增殖并检测微血管密度(MVD)。结果成功构建了子宫内膜异位种植的鸡胚模型。内异症实验组细胞的凋亡强度[(6.9±0.8)分]比内异症对照组[(5.4±1.1)分]明显增高,两组比较,差异有统计学意义(P<0.05);非内异症实验组细胞的凋亡强度[(6.7±0.9)分]也高于非内异症对照组[(5.0±0.9)分;P<0.05]。内异症实验组的 MVD[(4.9±1.2)条]比内异症对照组[(9.1±3.0)条]明显降低,两组比较,差异有统计学意义(P<0.05);非内异症实验组的 MVD[(4.2±1.1)条]也低于非内异症对照组[(6.9±1.6)条;P<0.05]。细胞增殖强度在各组间比较,差异无统计学意义(P>0.05)。结论异位子宫内膜鸡胚模型可作为研究异位子宫内膜血管形成及抗血管形成的动物模型;抗 VEGF 抗体可能是通过促进内膜细胞的凋亡,促进血管内皮细胞的凋亡,抑制血管形成从而达到抑制细胞种植、生长的目的,而对细胞的增殖无明显的抑制作用。Objective To establish the chick embryo chorioallantioc membrane （CAM） as a model for in vivo research on endometriosis. The model was used to investigate the mechanism of anti-vascular endothelial growth factor （VEGF） antibody for treatment of endometriosis. Methods Human endometrial fragments were explanted onto the CAM. Then anti-VEGF antibody was used for the endometriosis-like lesions after transplantation of human endometrial fragments. The CAM models were treated respectively as control groups and experimental groups. The terminal deoxynucleotidyl transferase-mediated biotindeoxyuridine triphosphate （dUTP） nick end labeling （TUNEL）, proliferating cell nuclear antigen （PCNA） and microvessel density （MVD） were used in vivo for analysis of anti-angiogenesis. Results The apoptosis intensity of anti-VEGF antibody treated groups （6.7 ±0. 9, 6. 9± 0. 8） was significantly higher than that of the control groups （5.0 ± 0. 9, 5.4± 1.1 ; P 〈 0.05 ）. The proliferation intensity was not different in these groups. Lower MVD was observed in experimental groups [ （ 4. 2 ±1.1 ）, （ 4. 9 ± 1.2 ） vessels ] than the control groups [ （6. 9±1.6）, （9. 1 ± 3.0） vessels ; P 〈 0.05 ]. Conclusions CAM is an extraembryonic membrane that is commonly used in vivo for the study of angiogenesis and anti-angiogenesis. Anti-VEGF antibody can be used to accelerate apoptosis of the endometrial cells and vascular endothelium cells, but it has no effect on the proliferation of these cells.

关 键 词：鸡胚 尿囊 子宫内膜异位症 血管内皮生长因子A 抗体 

分 类 号：R711.71[医药卫生—妇产科学]