军事医学2026，Vol.50Issue(5)：334-341,8.DOI:10.7644/j.issn.1674-9960.2025-00285
小分子化合物SB4减轻小鼠骨髓造血干/祖细胞的电离辐射损伤效应
Effects of SB4 on mitigation of radiation-induced mouse bone marrow hematopoietic stem and progenitor cell injury
陈彦州 1李允兴 2张博文 1李昀桥 1吕洋 1范韬 1徐彩萍 1李艳华1
作者信息
- 1. 军事科学院军事医学研究院,北京 100850
- 2. 军事科学院军事医学研究院,北京 100850||哈尔滨工业大学生命科学与技术学院,哈尔滨 150080
- 折叠
摘要
Abstract
Objective To investigate whether SB4,a bone morphogenetic protein 4(BMP4)signaling agonist,can alleviate ionizing radiation-induced damage to mouse bone marrow hematopoietic stem/progenitor cells(HSPCs).Methods Mouse bone marrow lineage-negative(Lin⁻)cells were isolated and cultured in vitro.The optimal concentration of SB4 was determined by detecting intracellular phosphorylated mothers against decapentaplegic homolog 1/5/9(p-SMAD1/5/9)expressions via flow cytometry and assessing cell viability via acridine orange/propidium iodide(AO/PI)staining.An in vitro ionizing radiation(IR)injury model was established by exposing Lin-cells to 3 Gy X-ray irradiation.Cells were divided into the irradiation alone group(IR-SB4 group)and the SB4 pretreatment followed by irradiation group(IR+SB4 group).On day 1 post-irradiation,flow cytometry was used to analyze the proportion and number of HSPCs and hematopoietic stem cells(HSCs).The percentage of γ-H2A histone family member X(γ-H2AX)-positive cells,levels of reactive oxygen species(ROS),and cysteinyl aspartate-specific protease 3(caspase-3)expressions in HSCs were also determined.Real-time quantitative PCR(qPCR)was used to detect the mRNA expression levels of antioxidant genes and the anti-apoptotic genes in HSPCs from both groups.Results The BMP4 signaling agonist SB4 effectively increased the phosphorylation of SMAD1/5/9 in mouse bone marrow hematopoietic cells,and 1 μmol/L was identified as the optimal concentration for HSPCs.Compared with the IR-SB4 group,the proportions and numbers of HSPCs and HSCs were significantly larger in the IR+SB4 group,along with a lower γ-H2AX-positive rate,reduced ROS accumulation,and downregulated caspase-3 expressions in HSCs.Meanwhile,the mRNA expression levels of key genes involved in antioxidative stress and anti-apoptotic pathways in HSPCs were upregulated.Conclusion SB4 can alleviate ionizing radiation-induced damage to mouse HSPCs.The underlying mechanism is possibly associated with the activation of SMAD1/5/9 phosphorylation and the upregulation of antioxidative stress and anti-apoptotic gene expressions in HSPCs.关键词
造血干/祖细胞/骨形态发生蛋白4信号激动剂SB4/辐射损伤/抗氧化应激Key words
hematopoietic stem and progenitor cells/BMP4 signaling agonist SB4/radiation injury/antioxidative stress分类
医药卫生引用本文复制引用
陈彦州,李允兴,张博文,李昀桥,吕洋,范韬,徐彩萍,李艳华..小分子化合物SB4减轻小鼠骨髓造血干/祖细胞的电离辐射损伤效应[J].军事医学,2026,50(5):334-341,8.
