期刊
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
卷 90, 期 1, 页码 36-44出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/09553002.2014.847294
关键词
Radiation-induced hematopoietic damage; gene therapy; hepatocyte growth factor
资金
- Chinese High-Tech (863 Program) [SS2012AA020408]
- Beijing Nova Program [Z121107002512122]
- National Natural Science Foundation of China [30900634, 30930041, 81072240]
Purpose : To investigate whether adenovirus-mediated delivery of the human hepatocyte growth factor (HGF) gene could prevent radiation-induced hematopoietic damage. Materials and methods : Thirty C57BL/6 mice were randomized into three groups, in which phosphate buff er saline (PBS), mock adenovirus vector (Ad-null) or adenovirus vector containing HGF (Ad-HGF) were injected into the tail vein of each group, respectively. After 48 hours, the mice received a single irradiation dose of 6.5 Gy Co-60 gamma rays. Blood samples were extracted via the tail vein at day 0, 4, 7, 10, 14, 21, 24 and 30 after irradiation, for red blood cell (RBC) and white blood cell (WBC) and cluster of differentiation4 (CD4)/cluster of diff erentiation8 (CD8) ratio assessment. At weekly intervals following irradiation, serum erythropoietin (EPO), Interleukin-6 (IL-6) and Interferon-gamma (IFN-gamma) levels were measured using enzyme-linked immunosorbent assay (ELISA). On post-irradiation day 30, the mice were autopsied and erythroid burst-forming units (BFU-E) were evaluated. Results : Adenovirus-mediated HGF gene transfer could increase human HGF level in serum and have a significant elevation in RBC and WBC count. Ad-HGF increased EPO and IL-6 levels and prompted BFU-E formation. Ad-HGF decreased radiation-induced micronucleus frequency in the mouse bone marrow (BM). Most evidence of radiation-induced hematopoietic damage was observed morphologically in bone marrow specimen four weeks after irradiation. Ad-HGF protected against radiation-induced BM failure and increased survival. Finally, Ad-HGF increased the thymic index and enhanced immune function in the irradiated C57BL/6 mice. Conclusions : This is the first report to date that demonstrates the potential of HGF gene transfer to prevent radiation-induced hematopoietic damage.
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