摘要
目的 :探讨恶性肿瘤MDRl基因治疗以保护骨髓造血细胞 ,从而加大化疗剂量 ,提高中晚期肝癌小鼠生存率。方法 :用培养的H2 2腹水型肝癌细胞注入Balb/c小鼠制成肿瘤模型 ,同种骨髓造血细胞经浓缩病毒上清法转染MDRl基因后 ,移植入预先照射亚致死剂量60 Co -γ射线的荷瘤小鼠 ,再经大剂量化疗 ,实验分为对照组及阿霉素 5mg/kg(最大剂量 )组、10mg/kg(2×最大剂量 )组、2 0mg/kg(4×最大剂量 )组 3个剂量组 ,分别在化疗 3天后观察小鼠白细胞的变化情况 ,取骨髓造血细胞做P -糖蛋白免疫组化以观察MDRl基因的表达情况 ;测定小鼠死亡率。结果 :化疗第 1、2周实验组白细胞明显高于对照组(P <0 .0 1) ,第 1周各剂量组之间无明显差别 (P >0 .0 5 ) ,第 2周 2 0mg/kg(4×最大剂量 )组比其它两组白细胞数偏低 (P <0 .0 5 )。 10mg/kg和 2 0mg/kg组死亡率明显低于对照组 (P <0 .0 1)。实验组免疫组化阳性率为 8.6 3%± 0 .36 % ,而对照组为零。结论 :MDR1基因转染骨髓造血干细胞后 ,使其对阿霉素的耐受性增加。
Objective:The study was to improve the protection of the bone marrow during the chemotherapy of late hepatocarcinoma balb/c mice and increase its survival rate. Methods:Cultivated H22 hepatocarcinoma cell was injected into the balb/c mouse to make the animal model. MDR1 gene was transferred into the hematopoietic cells of murine bone marrow by the mediation of retrovirus vecter and transplanted into the balb/c mouse with hepatocarcinoma exposure with 60 Co-γ ray in advance.WBC were investigated 3 days after high-dose chemotherapy. The function and the expression of MDR1 gene were detected by PCR method and IC method in vitro and in vivo. Results:WBC of the different dose experiment group was higher than that of the control group obviously ( P <0.01).In the first week the counting of WBC of the different dose experiment group was not obviously different( P >0.05) ,but in the second week WBC counting of the 0.8mg/kg group was lower than that of the other two groups( P <0.05).The mortality rate of 0.4mg/kg and 0.8mg/kg was lower than that of the control group( P <0.05).P-gp positive staining rate of the experiment group was 8.63±0.36%,and the control group was zero.Conclusion:MDR1 gene transplanted into the body of balb/c mice with hepatocarcinoma during the chemical treatment of the Balb/C mice with hepatocarcinoma can proctect the bone marrow and extend the survival time.
出处
《重庆医科大学学报》
CAS
CSCD
2003年第5期580-584,共5页
Journal of Chongqing Medical University
基金
国家自然基金资助项目NO .3 0 0 70 781
关键词
基因治疗
多药耐药
阿霉素
肝癌
骨髓移植
Gene therapy
Multidrug resistance
Doxorubicin
Hepatocarcinoma
Marrow transplant
