多药耐药基因转染对荷瘤小鼠骨髓造血细胞的保护作用

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。

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

Objective To observe the distribution of bone marrow mononuclear cells (BM-MNCs) after the transfection of exogenous multi-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 salin...