超剂量化疗治疗mdr1基因转染骨髓移植的VX2肝癌兔疗效和毒副作用研究  

Research on the effects and side effects of the over-dose chemotherapy to VX2 hepatocarcinoma rabbits with mdr1 gene transferring bone marrow transplantation

作　　者：王佚[1] 金先庆[1] 王荞[2] 罗庆[1] 罗小辑[1] 

机构地区：[1]重庆医科大学附属儿童医院普外科,重庆400014 [2]重庆医科大学附属儿童医院超声科,重庆400014

出　　处：《重庆医科大学学报》2006年第5期645-648,共4页Journal of Chongqing Medical University

基　　金：国家自然科学基金重点项目(30330590)

摘　　要：目的:mdr1基因转染的骨髓造血细胞自体移植后,观察VX2肝癌兔超剂量化疗中mdr1基因的骨髓保护及肿瘤治疗作用;并观测超剂量化疗对心脏的毒副作用。方法:mdr1基因转入兔骨髓单个核细胞并自体移植;阿霉素化疗,观测外周血白细胞数、VX2肝肿瘤的生长及转移、心脏结构和功能变化,评价mdr1基因对受体骨髓的保护作用、超剂量化疗对肿瘤的治疗作用及对心脏的毒副作用。结果:通过转染的自体骨髓移植将mdr1基因导入受体骨髓;超剂量阿霉素化疗后,实验组荷瘤兔外周血白细胞可维持在(4.26±1.03)×109/L,肿瘤能被有效杀灭,荷瘤动物的生存时间明显高于对照组(P<0.05);同时也观察到超剂量化疗对心脏的严重损害。结论:mdr1基因能明显提高骨髓对化疗的耐受性;超剂量化疗能有效杀灭肿瘤,同时也对非造血系统脏器造成严重损害。Objective： In the study, multidrug resistance gene 1 （mdrl） was transferred into the bone marrow mononuclear cells which were autotransplanted into rabbits with VX2 hepatocarcinoma. In chemotherapy experiment with adriamycin, the bone marrow protection of mdrl gene, curative effects and side effects to heart of over dosage chemotherapy were observed. Methods： The bone marrow mononuclear ceils transferred with mdrl gene were autotransplanted into rabbits with VX2 hepatocarcinoma. After chemotherapy with adriamycin, the peripheral white blood ceils count, the growth and metastasis of VX2 hepatocarcinoma and cardiac function were detected. Meanwhile, the bone marrow protection of mdrl gene, the curative effects to VX2 bepatocarcinoma and lesions to heart of over-dosage chemotherapy were evaluated. Results：The mdrl gene was implanted into the bone marrow after the mdrl-transferred bone marrow mononuclear cells had been autotransplanted into rabbits with VX2 hepatocarcinoma. After over-dose chemotherapy with adriamycin, the rabbits in mdrl-transferring group could be survival after treated with 3-fold dosage chemotherapy, and the white blood cell count in peripheral blood was （4.26±1.03）×10^9/L. Meanwhile, the tumor cells were killed effectively, and the survival time were improved compare to that of control group （P〈0.05）.However, the severe lesions to heart caused by over dosage chemotherapy were observed. Conclusions： The bone marrow of the receptor could be protected from toxic effects of chemotherapy after transplantation of bone marrow mononuclear cells transferred with mdrl gene, and the malignant tumor cells could be killed effectively and severe lesions to non-hematopoietic systems were caused by over dosage chemotherapy.

关 键 词：MDRL基因 骨髓造血细胞 化疗 肝癌 

分 类 号：R394[医药卫生—医学遗传学]