MDR1基因转染的骨髓单个核细胞对放疗后造血功能重建的研究

Investigation of post-radiotherapeutic hematopoietic reconstruction mediated by multidrug resistance gene 1 transfected bone marrow mononuclear cells

目的研究BALB／c小鼠放射治疗后经尾静脉回输携带多药耐药MDRl基因的骨髓单个核细胞（bone marrow mononuclear cells，BM-MNCs）对造血功能重建的影响。方法BALB／c近交系小鼠32只，随机分为4组：正常对照组、空白对照组、阴性对照组和实验组。正常对照组不做任何处理，其他3组首先接受1．5Gy^60Co-γ射线全身照射，空白对照组尾静脉回输等量生理盐水，阴性对照组经尾静脉回输未转染MDR1基因BM-MNCs，实验组回输已转染MDR1基因BM-MNCs。动态观察各组外周血变化。结果同种异体回输后第七天，阴性对照组和实验组与空白对照组比较均表现为白细胞恢复提前。实验组7、10、14d白细胞计数分别为（2．9±0．3）×10^9／L、（3．2±0．2）×10^9／L、（4．2±0．3）×10^9／L，阴性对照组为（2．7±0．2）×10^9／L、（2．8±0．2）×10^9／L、（3．5±0．3）×10^9／L，实验组与阴性对照组比较，白细胞数量增加，差异有统计学意义（t=2．21、3．53、4．73，P〈0．05），14d后差异无统计学意义（t=0．79，P〉0．05）。结论同种异体携MDR1基因的骨髓单个核细胞移植，能在早期显著提高外周血白细胞数量，利于骨髓造血微环境恢复，加快辐射损伤后骨髓早期造血功能重建。

Objective To investigate the post-radiotherapeutic hematopoietic reconstruction me- diated by multidrug resistance gene 1 （MDR1） transfected bone marrow mononuelear cells （BM- MNCs）. Methods Thirty-two BALB/c mice were randomly divided into four groups （n = 8/group） ： normal group, blank control group, negative control group and transfection group. Mice in the blank control group, negative group and transduced group accepted 1.5Gy^60Co-γ radiotherapy. After radiotherapy, normal BM MNCs were given to mice in the blank control group; normal saline was given to mice in the negative control group by tail vein injection; MDR1 transfected BM-MNCs were given to mice in the transduced group by tail vein injection. The following peripherals blood changes in each group were observed and determined dynamically. Results The number of the peripheral leukoeytes in mice of the negative and transfected group increased significantly compared with that in the blank control group on the seventh day after injection. The number of the peripheral leukocytes in mice of the transfected group increased significantly compared with those in negative control group on day 7, 10 and 14 after injection （2.9 ± 0. 3 ×10^9/L vs 2. 7 ± 0. 2 ×10^9/L, t = 2. 21, P〈0. 05; 3. 2 ± 0. 2 ×10^9/L vs 2.8±0.2×10^9/L t = 3.53, P〈0.05; 4.2 ±0.3×10^9/L vs 3.5 ±0.3×10^9/L, t=4. 73, P〈 0. 05）. There was no statistical difference between three groups after 14 days （t = 0. 79, PT〉0. 05）. Conclusions MDR1 transfected BM-MNCs can significantly inerease the count of peripheral white blood cells in a short period and improve the hemopoietic microenvironment of bone marrow, thus it can promote the post-radiotherapeutic hematopoietic reconstruction.