白细胞介素－11基因治疗促进放射损伤小鼠造血恢复的实验研究

Effects of interleukin-11 gene therapy on hematopoiesis of irradiated mice

白细胞介素－１１（Ｉｎｔｅｒｌｅｕｋｉｎ－１１，ＩＬ－１１）是一种新的造血生长因子，体内、外实验结果显示ＩＬ－１１具有显著的造血促进作用，它能作用于早期的造血干细胞及祖细胞，促进其增殖和分化。为了探讨ＩＬ－１１基因治疗放射损伤后造血恢复的促进作用，我们构建了含人ＩＬ－１１ｃＤＮＡ的逆转录病毒载体，并转染小鼠成纤维细胞系ＮＩＨ－３Ｔ３，经筛选获得３株高表达ＩＬ－１１的转染细胞亚克隆，用高表达ＩＬ－１１的转染细胞作为载体细胞，进行了ＩＬ－１１基因治疗对放射损伤小鼠造血系统影响的实验研究。结果表明ＩＬ－１１基因治疗能明显缩短亚致死量放射损伤小鼠白细胞降低的时间，促进外周血白细胞、血小板和红细胞压积的恢复。提示ＩＬ－１１基因治疗对放射损伤造成的造血功能低下具有潜在的应用价值。

interleukin-11 is a multifunctional hematopoietic growth factor, especially in hematopoiesis. It can act synergistically with IL-3 to stimulate hematopoiesis at multiple stages by shortening the G_0 period of hematopoietic progenitor cells, and has a very strong effect on increasing perpheral platelet level. This fact suggests that IL-11 might be a potential hematopoiesis-promoting drug. In order to identify the availability of IL-11 gene therapy in hematopoiesis disorders, a retroviral vector carrying IL-11 cDNA was constructed and transfected into murine fibroblast cell line NIH-3T3. After G418 selection and cloning, we obtained a subclone 1E7 secreting high level of IL-11, and we transplanted 1E7 cells intraperitoneally into BALB/c mice to inverstigate its effects on peripheral blood cell count and bone marrow colony formation of sublethally irradiated mice. Results showed that IL-11 gene therapy had significant effects on both normal and sublethally irradiated mice including an increase in the peripheral platelets of normal mice and marked acceleration of the recovery of peripheral WBC and platelets in sublethally irradiated mice. This results suggested that IL-11 might play an important role in the regulation of hematopoiesis and IL-11 gene therapy had a potential value in hematopoiersis recovery.