外源血小板生成素基因体内导入对循环免疫因子水平的影响

赵建增　刘　丽　梅英杰　

　　中国图书分类号　Q511　R392.12　R392.11
　　摘　要　目的：研究外源TPO基因由质粒载体导入后，小鼠体内一些细胞因子的变化规律。方法：用脂质体将表达人TPO的真核表达质粒pcDNA3/hTPO包裹后，注射到Balb/c鼠的后肢肌肉内，用ELISA法检测小鼠血液中多种细胞因子的水平。结果：在TPO cDNA转移到体内后，血液中IFN-γ、TNF-α和IL-2迅速升高。其中，IFN-γ与血小板计数呈明显负相关，并且在血小板计数回落后，保持在对照水平的9～12倍；TNF-α仅在第1周内与之成正相关，但可达对照水平的120倍；IL-2升高幅度较小，与TPO水平相一致。血液中Ⅱ型组织相容性抗原分子也呈升高趋势，与IL-2的变化类似 ；而Ⅰ型分子与TNF-α的变化相似。结论：TPO在多方面刺激了机体免疫机能，而免疫因子如IFN-γ在血小板生成过程中起重要的调节作用。
　　关键词　血小板生成素　免疫调节　IFN-γ　TNF-α　IL-2　组织相容性抗原

Effect of thrombopoietin gene delivery on the concentration of serum cytokines in mice

ZHAO Jian-Zeng,LIU Li,MEI Ying-Jie.
Laboratory of Gene Therapy,Center for Clinical Molecular Biology,General Hospital of Air Force,Beijing 100036

　　Abstract Objective：To investigate the effect of TPO on the expression of cytokines.Methods：The liposome-coated DNA of plasmid pcDNA3 carring human thrombopoietin(TPO) cDNA was intramuscularly administered into Balb/c mice.The serum cytokine levels were determined using ELISA.Results:Soon after the gene delivery,serum IFN-γ,TNF-α and IL-2 abruptly increased.IFN-γ level was negatively associated with platelet count(PLTC) in the stage of PLTC declination,it reached to 9～12 folds more than that of the controls.Although TNF-α level had reached 120 folds more than that of the control in the first week,positively associated with the PLTC. The increase of IL-2 was not significant. Furthermore,class Ⅱ molecules of major histocompatibility were also increased, while class I molecules showed no significant changes except the first week.Conclusion:TPO might participate in immunoregulation.And IFN-γ might play key role in down regulation of the thrombopoiesis.
　　Key words Thrombopoietin Immunoregulation IFN-γ TNF-α IL-2 Histocompatibility antigens

　　一般认为，血小板生成素(TPO)是巨核系特异的促生长因子，由于分子结构与EPO有高度的同源性，它同样能诱导粒/巨核系集落形成单位和红系爆式集落形成单位的增生。另外，不仅在巨核系细胞中，

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