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目的：探讨联合应用成纤维细胞介导ＩＬ２和ＩＬ３的基因疗法对骨髓移植（ＢＭＴ）后荷瘤小鼠抗肿瘤作用的效果及机理。方法：将分别转染ＩＬ２基因及ＩＬ３基因的ＮＩＨ３Ｔ３细胞以单独或联合方式移植至ＢＭＴ的荷瘤小鼠腹腔内８ｄ后，取出小鼠骨髓细胞检测杀伤活性的变化以及ＩＬ２受体的表达，并观察荷瘤小鼠的存活期。结果：ＩＬ３基因治疗虽然可加速ＢＭＴ后造血重建过程，但对骨髓细胞的ＮＫ、ＬＡＫ活性具有一定的抑制作用；ＩＬ２基因治疗可明显提高骨髓细胞的杀伤活性；联合应用基因治疗后荷瘤小鼠骨髓ＮＫ、ＬＡＫ活性及骨髓细胞ＣＤ２５表达升高，明显延长大剂量化疗后接受ＢＭＴ的荷瘤小鼠的存活期。结论：联合应用ＩＬ２和ＩＬ３的基因疗法能协同提高骨髓细胞ＩＬ２受体表达水平，提高骨髓细胞毒活性，增强ＢＭＴ后的抗肿瘤效果。
OBJECTIVE: To investigate the effect and mechanism of combined gene therapy of fibroblast-mediated IL-2 and IL-3 on tumor-bearing mice after bone marrow transplantation (BMT). METHODS: NIH3T3 cells transfected with IL-2 gene and IL-3 gene were transplanted into the peritoneal cavity of BMT tumor-bearing mice individually or in combination. After 8 days, the mouse bone marrow cells were taken out for detection of changes in killing activity and IL-2. Expression of receptors and observation of the survival of tumor-bearing mice. Results: IL3 gene therapy can accelerate the hematopoietic reconstitution after BMT, but it has a certain inhibitory effect on NK and LAK activity of bone marrow cells; IL2 gene therapy can significantly improve the killing activity of bone marrow cells; after combined use of gene therapy The activity of NK and LAK in bone marrow and the expression of CD25 in myeloid cells were increased in tumor-bearing mice, which significantly prolonged the survival of tumor-bearing mice receiving BMT after high-dose chemotherapy. Conclusion: The combination of IL 2 and IL 3 gene therapy can synergistically increase the expression of IL 2 receptor in bone marrow cells, increase the cytotoxicity of bone marrow, and enhance the antitumor effect of BMT.