抗血管生成抑制裸鼠异位子宫内膜的生长
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Inhibition effect of an antiangiogenesis therapy on endometrium growth in a nude mouse model
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    目的:研究抗血管生成对裸鼠异位子宫内膜病灶的抑制作用-方法:利用腺病毒AdEasy-1系统及AAV293细胞构建携带内皮抑素(ES)基因的重组腺病毒Ad-ES,体外感染脐静脉内皮细胞ECV-304,诱导其凋亡;建立人子宫内膜裸鼠皮下种植模型,将Ad-ES-空载腺病毒Ad-Track及生理盐水分别注射至裸鼠皮下病灶,观察病灶的形态学特点,检测微血管密度(MVD),TUNEL法检测血管内皮细胞及腺细胞凋亡-结果:Ad-ES经测序-PCR鉴定构建成功,滴度为2.06×1010 pfu/ml;ECV-304感染Ad-ES后,流式细胞术及Hoechest 33258染色均检测到细胞凋亡;成功建立人子宫内膜裸鼠皮下种植模型,Ad-ES治疗组病灶体积较其他两组明显缩小(P < 0.05),HE染色后,光镜下可见腺体萎缩明显,部分结构不完整,间质伴有不同程度的坏死,TUNEL法检测到细胞凋亡明显增加,MVD减少-结论:内皮抑素可诱导血管内皮细胞凋亡-抗血管生成,并可抑制裸鼠异位子宫内膜病灶的生长,抗血管生成可能作为治疗子宫内膜异位症的方法-

    Abstract:

    Objective: To investigate the effect of an antiangiogenesis therapy on inhibition of endometrium growth in the nude mouse model. Methods:Recombinant adenovirus was constructed with AdEasy-1 system and AAV 293 cells. Apoptosis of ECV-304 cells was induced by Ad-ES and growth inhibition was observed. The nude mouse endometriosis model was established by subcutaneous implantation. Injected in local focus with Ad-ES,Ad-Track or physiologic saline, the ectopic focuses were detected by microscopy after HE staining. The microvessel densities (MVD) were detected by immunohistochemistry and the apoptosis were detected by TUNEL. Results:The conduction of Ad-ES was proved by PCR, and titer of Ad-ES was 2.06×1010 pfu/ml. The apoptosis of ECV-304 cells induced by Ad-ES was analyzed by flow cytometer and Hoechst 33258 staining. The nude mouse endometriosis model was established by subcutaneous implantation, and the volume of endometriotic lesions treated by Ad-ES was deminished significantly compared with the other two control groups (P < 0.05). MVD and the apoptosis were decreased significantly in the group using Ad-ES compared with the two control groups. Conclusion:ES can induce ECV-304 cells to apoptosis and can inhibit the growth of endometrium in the nude mouse model. Antiangiogenesis may be a potential way for therapy of endometriosis.

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马 颖,何援利.抗血管生成抑制裸鼠异位子宫内膜的生长[J].南京医科大学学报(自然科学版),2010,(11):1599-1603

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  • 收稿日期:2010-05-22
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