构建携小鼠内皮抑素(endostatin， ES )基因的重组腺病毒载体，观察其对荷骨肉瘤裸鼠肺转移的抑制，探讨内皮抑素表达水平与骨肉瘤肺转移的关系。方法:构建pDC315 mEndo表达质粒，同源重组产生重组腺病毒Ad mEndo。裸鼠右前肢皮下注射骨肉瘤MG 63细胞建立移植瘤裸鼠模型；随机分为4组：小鼠内皮抑素腺病毒（Ad mEndo）组，携带EGFP基因腺病毒（Ad EGFP）组， PBS组，未接种肿瘤细胞裸鼠空白对照组。各组裸鼠每周分别注射相应药物200 μl，连续5次，观察各组动物移植瘤体积、瘤组织病理，ELISA法检测各组裸鼠血ES水平；7周后处死动物，观察有无肺转移及肺转移灶病理。结果：Ad EGFP组肿瘤体积为（1.53±0.05） cm 3,PBS组为（1.56±0.07） cm 3, Ad mEndo组为（0.91±0 .03） cm 3， Ad mEndo 治疗的抑瘤率达40.7％。Ad mEndo组裸鼠血内皮抑素表达水平明显高于Ad EGFP组和PBS组（ P <0.05）。Ad mEndo组裸鼠肺部未发现肿瘤转移灶，其他两组肺部见大量散在转移灶，肺转移率分别为80%和90%。未发生肺转移裸鼠的ES水平显著高于发生肺转移的裸鼠（ P <0.05）。结论：腺病毒介导的小鼠内皮抑素显著抑制了荷骨肉瘤裸鼠肺转移，内皮抑素表达水平与肺转移有着直接的关系。

To construct an adenovirus mediated mouse endostatin vector (Ad mEndo) and to observe its inhibitory effect on the pulmonary metastasis of osteosarcoma in nude mice, so as to discuss the relationship between ES expression and the pulmonary metastasis of osteosarcoma. Methods: Recombinant adenovirus plasmid pDC315 mEndo was constructed and used to prepare recombinant Ad mEndo. Osteosarcoma MG 63 cells were subcutaneously injected into the right fore limbs to establish nude mouse model of osteosarcoma; and the models were randomly divided into 3 groups: Ad mEndo group, Ad EGFP group and PBS group; animals receiving no transplantation served as blank control. The corresponding agents were injected (20 μl per time) for a consecutive of 5 times on a weekly basis. The tumor volumes, histopathological characteristics were observed; ELISA was employed to examine the serum ES level. Animals were sacrificed 7 weeks later and the pulmonary metastasis was observed. Results: Sixteen days later，the tumor volume was (1.53±005)cm 3 in Ad EGFP group, (1.56±0.07)cm 3 in the PBS group, and (0.91±0.03)cm 3 in the Ad mEndo group, with the tumor inhibitory rate being 40.7％ in the last group. The serum ES level in the Ad mEndo group was significantly higher than that of the other groups ( P <0.05). No pulmonary metastasis was noticed in the Ad mEndo group, but extensive metastases were seen in the lungs of the other 2 groups, with the metastasis rates being 80% and 90%. Mice without metastasis had significantly higher levels of ES compared with those with metastasis ( P <0.05). Conclusion: Adenovirus mediated mouse endostatin can significantly inhibit the pulmonary metastasis of osteosarcoma in nude mice, indicating a directly link between expression of ES and pulmonary metastasis.

国家自然科学基金资助项目（No.30471760）