南方医科大学学报 ›› 2015, Vol. 35 ›› Issue (02): 281-.

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慢病毒介导靶向survivin基因的shRNA抑制子宫内膜在裸鼠腹腔种植生长

彭冬先,何援利   

  • 出版日期:2015-02-20 发布日期:2015-02-20

Lentiviral vector-mediated short hairpin RNA targeting survivin inhibits abdominal
growth of human endometrium xenograft in nude mice

  • Online:2015-02-20 Published:2015-02-20

摘要: 目的研究慢病毒介导生存素(survivin)基因特异性短发夹状RNA(shRNA) 对人子宫内膜在裸鼠腹腔种植生长的影响。
方法将45只裸鼠随机分为实验组、阴性对照组及空白对照组,每组15只,将子宫内膜异位症患者在位内膜注射入裸鼠腹腔,同
时将survivin-shRNA慢病毒、空载慢病毒及磷酸盐缓冲液分别注射至3组裸鼠腹腔内,2周后观察各组子宫内膜种植成功率,光
镜下观察异位病灶的形态学特点,免疫组化方法检测各组病灶中survivin 的表达水平。结果实验组子宫内膜种植成功率
(26.67%)明显低于阴性对照组(73.33%)及空白对照组(80%,P<0.01);实验组成活的异位内膜腺体发育不良,间质伴有不同程
度的坏死;该组病灶中survivin蛋白表达亦明显下降,与两对照组比较差异有显著性(P<0.001)。结论慢病毒介导survivin基因
特异性shRNA能够通过靶向沉默survivin基因明显抑制人子宫内膜在裸鼠腹腔中的种植生长。

Abstract: Objective To investigate the inhibitory effect of lentiviral vector-mediated short hairpin RNA targeting survivin
(LV-survivin shRNA) on the growth of human endometrium xenograft in the abdominal cavity of nude mice. Methods The
endometrium xenografts from 8 women with endometriosis were injected into the peritoneal cavities of 45 nude mice. The
mice were then randomly assigned to receive intraperitoneal injection of LV-survivin shRNA, pGCL-NC-GFP (negative
control) or PBS (blank control). Two weeks later, the number and morphometry of endometriotic lesions were quantified and
the expression of survivin protein were detected by immunohistochemistry. Results The formation of endometriotic lesions
was significantly suppressed in mice receiving LV-survivin shRNA injection as compared with those in the two control groups
(P<0.001). The mice in LV-survivin-shRNA group showed significantly down-regulated expression levels of survivin protein
compared with those in the negative and blank control groups, presenting also necrosis in the endometriosis-like lesions in
microscopic observation. Conclusion Lentiviral vector-mediated shRNA can effectively inhibit the expression of survivin in
human endometrium xengrafts and suppress the formation and growth of endometriotic lesions in the abdominal cavities of
nude mice.