突变的MTX耐药基因对骨髓造血干细胞的保护作用

PROTECTION OF BONE MARROW HEMOPOIETIC STEM CELLS BY MTX RESISTANT GENE

目的研究转染耐药基因后对造血干细胞的保护作用方法以脂质体为载体，把二氢叶酸还原酶（ＤＨＦＲ）突变的对氨甲喋呤（ＭＴＸ）耐药的基因转染到小鼠造血干细胞，再输回至小鼠体内后，对小鼠进行为期９周的大剂量ＭＴＸ化疗。结果转染ＭＴＸ耐药基因组小鼠化疗前后的粒细胞总数及体重均较稳定，而未转染基因组小鼠的粒细胞总数及体重呈明显下降（Ｐ＜０．０５）。小鼠存活率在转染基因组较对照组有明显提高。从小鼠脾脏提取ＤＮＡ，经ＰＣＲ扩增后，证实转染基因组有耐药基因的高效表达。结论此实验为肿瘤患者在大剂量化疗时，进行保护造血功能，提高化疗疗效的实验研究和临床应用，提供有参考价值的资料。

Objective:Protection of bone marrow hemopoietic stem cells(HSC) by transfected MTX resistant gene was studied.Methods:A mutant MTX resistant gene was transfected into murine HSC with liposome as the vector. The cells were then infused into mouse again. The mice were injected with high dose of MTX. Results:The WBC counts and weights of the mice transfected with MTX resistant gene were rather stable,but a declining tendency was obviously existed in the untransfected groups ( P <0 05). Survival rate was higher in the transfected group and the MTX resistant gene expression in extracted spleen DNA of transfected mice was demonstrated by PCR. Conclusion:This result provided a valuable data for experimental and clinical research on protecting the bone marrow hemopoietic function and enhancing the effectiveness of chemotherapy in cancer patients.