多药耐药基因转染对荷瘤小鼠骨髓造血细胞的保护作用  

MDR1 gene transfection protects haematogenesis of bone marrow cells in tumor-bearing mouse

作　　者：张秀亚[1] 王珊[1] 李圆[1] 孔祥如[1] 王江波[1] 

机构地区：[1]重庆医科大学附属儿童医院肿瘤外科,重庆400014

出　　处：《第三军医大学学报》2008年第23期2164-2167,共4页Journal of Third Military Medical University

基　　金：国家自然科学基金(30471801)~~

摘　　要：目的探讨MDR1基因转染荷瘤小鼠骨髓单个核细胞(BM-MNCs)后在体内的分布和对骨髓造血细胞的作用。方法将32只H22肝癌荷瘤BALB/c小鼠随机分为4组:正常对照组(不照射不回输)、空白对照组(照射并回输生理盐水)、阴性对照组(照射并回输未转染的BM-MNCs)、转染实验组(照射并回输已转染的BM-MNCs),每组8只。阿霉素超剂量化疗,监测化疗过程中各组外周血细胞和肿瘤体积的变化,用RT-PCR法和免疫组化法检测外源性人MDR1基因和P-gp在荷瘤小鼠体内的表达和分布。结果化疗后各组红细胞和血小板均无明显变化,差异无统计学意义(P>0.05);转染实验组白细胞数于化疗后第4周降至(3.32±0.26),与化疗前(6.64±0.39)相比减少有统计学意义(P<0.05),化疗后第3周起转染实验组白细胞数高于阴性对照组,增高有统计学意义(P<0.05);化疗3周后与3个对照组相比转染实验组肿瘤体积较小,减小有统计学意义(P<0.05);外源性人MDR1基因和P-gp在骨髓和外周血单个核细胞有表达和分布,在心、肝、肺、脾和肾等组织中无表达和分布;肿瘤组织中无外源性人MDR1基因分布,有P-gp表达。结论MDR1基因转染荷瘤小鼠BM-MNCs后在超剂量化疗中对骨髓造血功能有保护作用,外源性MDR1基因在心、肝、肺、脾和肾等组织中无表达。Objective To observe the distribution of bone marrow mononuclear cells （ BM-MNGs） atter the transfection of exogenous muhi-drug resistance gene-1 （ MDR1 ） and its protective effect on the haematogenesis in bone marrow cells in gene therapy. Methods Thirty-two BALB/c tumor-bearing mouse were randomly and equally divide into 4 groups, normal control （ A）, blank control （ B）, negative control （C） and transfection control（D）. The animals of last 3 groups received a radiation of 1.5 Gy and then infusion of normal saline, untransfected and transfected BM-MNCs respectively. Normal control group underwent no treatment. After chemotherapy of overdose adriamycine, their peripheral blood （PB） ceils were counted and the tumor volume was measured. The distribution and expression of exogenous human MDR1 and P-gp by were detected by RT-PCR and immunohistochemistry. Results No difference was observed on the red cell and platelet count after chemotherapy （P 〈 0.05）. The white cell count of group D was decreased to （3.32 ±0.26） after 4 weeks＇ chemotherapy, significantly lower than that of pre-chemotherapy （6.64±0.39 ） （P 〈 0.05 ）. The white cell count was higher in group D than in group C after 3-week chemotherapy （P 〈 0.05）, and the tumor growth was slower in the group D （P 〈 0.05）. The MDR1 and P-gp expression was detected in bone marrow and PB mononuclear cells. There was no MDR1 and P-gp expression in the heart, liver, lung, spleen and kidney. There was P-gp but not MDR1 expression in the tumor mass. Conclusion The transfection of MDR1 gene into tumorbearing mice BM-MNCs may provide chemoprotection for BM haemopoiesis to some extent.

关 键 词：多药耐药基因 P-糖蛋白 骨髓单个核细胞 BALB/C小鼠 肿瘤 

分 类 号：R331.22[医药卫生—人体生理学] R73-362[医药卫生—基础医学]