Chen J-J, Gao Y, Tian Q, Liang Y-M, Yang L
1 Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Br J Radiol. 2014 Aug;87(1040):20140184. doi: 10.1259/bjr.20140184. Epub 2014 Jun 12.
The aim of this study was to find a new radiation protector, platelet factor 4 (PF4) and to identify its effect on haemopoietic microenvironment in vitro and in vivo.
Radiation damage on bone marrow mesenchymal stem cells ex and in vitro was set up as models. Growth curve analysis, clonogenic survival assay, FACSCalibur™ (BD Immunocytometry Systems, San Jose, CA), 5-ethynyl-2'-deoxyuridine immunofluorescence staining and quantitative reverse transcription-polymerase chain reaction were employed to assess the characterization of bone marrow mesenchymal stem cells (BMSCs), proliferation, apoptosis, cell cycle and gene expression.
A dose- and time-dependent enhancement of cell viability and survival was observed for PF4 treatment along with 500 cGy γ-radiation in vitro. The same phenomena were noted in vivo, including enhancement of adherence and proliferation ability while inhibition of cell apoptosis, which were associated with a short-term decrease in the G0/G1 ratio owing to S phase arrest. These were accompanied with enhanced Bcl-2 expression and p53/p21 loss.
These results uncover that PF4 might be a novel therapeutic approach, which could reduce DNA damage and increase survival of BMSCs, in part, by inhibiting p53/p21 axis and facilitating DNA damage repair.
This study explores the feasibility of a new radioprotector and hence may be clinically important.
本研究旨在寻找一种新的辐射防护剂——血小板因子4（PF4），并确定其在体内外对造血微环境的影响。
建立体外和体内骨髓间充质干细胞辐射损伤模型。采用生长曲线分析、克隆形成存活试验、FACSCalibur™（BD免疫细胞分析系统，加利福尼亚州圣何塞）、5-乙炔基-2'-脱氧尿苷免疫荧光染色和定量逆转录-聚合酶链反应来评估骨髓间充质干细胞（BMSCs）的特性、增殖、凋亡、细胞周期和基因表达。
在体外，PF4处理联合500 cGy γ射线照射后，观察到细胞活力和存活率呈剂量和时间依赖性增强。在体内也观察到相同现象，包括黏附能力和增殖能力增强，同时细胞凋亡受到抑制，这与由于S期阻滞导致的G0/G1比值短期下降有关。这些现象伴随着Bcl-2表达增强和p53/p21缺失。
这些结果表明，PF4可能是一种新的治疗方法，它可以部分通过抑制p53/p21轴并促进DNA损伤修复来减少DNA损伤并提高BMSCs的存活率。
本研究探索了一种新的辐射防护剂的可行性，因此可能具有临床重要性。
