摘要
目的探讨多药耐药基因转染小鼠骨髓单个核细胞移植后，化疗时其在体内的表达、分布以及在骨髓和外周血的富集效应。方法骨髓造血细胞转染外源性多药耐药基因后移植入荷瘤Balb／c小鼠，免疫组化和RT-PCR观察mdr1基因在骨髓造血细胞、外周血单个核细胞及重要脏器的表达和分布；监测外周血白细胞变化及肿瘤组织P-糖蛋白表达。结果外源性多药耐药基因在重要脏器和肿瘤组织无表达；化疗前骨髓细胞和外周血的P-糖蛋白表达阳性率分别为（9．36±1．84）％、（8．52±1．26）％，化疗药物剂量递增时，P-糖蛋白表达阳性率增高；移植未转染组与移植转染组外周血白细胞计数差异有统计学意义（P〈0．01）。结论外源性多药耐药基因转染在骨髓造血细胞和外周血单个核细胞有持续较高表达，在重要脏器无表达；随化疗药物剂量递增时骨髓和外周血有明显的富集效应；多药耐药基因转染介导保护骨髓在超剂量化疗中获得显著效果。
Objective To observe the distribution and enrichment of the foreign multidrug resistance gene 1 （mdrl） in the bone marrow mononuclear cells and peripheral blood in the liver cancer mice with intensive chemotherapy. Methods The bone marrow mononuclear cells which transferred with retrovirus-mediated mdrl were transplanted into Balb/c mice with liver cancer. The expression and distribution of foreign mdrl in the bone marrow mononuclear cells, peripheral blood mononuclear cells and chief organs were detected by irrtmunohistochemistry and reverse transcriptase polymerase chain reaction （RT-PCR）. And the peripheral white blood cells counting and the expression of P-glucoprotein in the tumors were monitored. Results There was no expression of mdrl in chief organs and tumors. However, the expression of mdrl was noted in bone marrow mononuclear cells and peripheral blood mononuclear cells. The expression rates of P-glucoprotein in bone marrow mononuclear cells and peripheral blood mononuclear cells were 9. 36 ±1.84% and 8. 52 ±1.26% before chemotherapy, and it was increased gradually along with intensified chemotherapy. The peripheral white blood cells counting after chemotherapy in the transferred mdrl gene group were significantly higher than those in the control group （P〈0. 01）. Conclusions The mdrl can be expressed in bone marrow mononuclear cells and peripheral blood mononuclear cells. The mdrl gene therapy may provide some degrees of protection of bone marrow to increase the chemotherapy dose to kill tumor cells.
出处
《中华小儿外科杂志》
CSCD
北大核心
2008年第4期246-250,共5页
Chinese Journal of Pediatric Surgery
基金
国家自然科学基金资助项目（编号：30471801）
关键词
基因
MDR
骨髓移植
基因疗法
肿瘤
Genes, MDR
Bone marrow transplantation
Gene therapy
Neoplasms
