山东医药2018，Vol.58Issue(8)：26-30,5.DOI:10.3969/j.issn.1002-266X.2018.08.007
Notch信号途径对放疗后骨髓谱系造血重建的影响及其机制
Effect of Notch signaling pathway on bone marrow pedigree hematopoietic reconstruction after radiotherapy
摘要
Abstract
Objective To investigate the effect of Notch signaling pathway on hematopoietic reconstruction of bone marrow pedigree after radiotherapy, and to explore its possible mechanism. Methods The double transgenic mice MxCre + RBP-Jflox/flox (knockout group) and control mice MxCre + RBP-Jflox/ + (non-knockout group) were generated to conditionally disrupt Notch signaling in the bone marrow. Mice were subjected to total body irradiation with γ-ray from a 60Co irradiator. We observed the hematopoietic reconstitution on the 7th day after irradiation. The C57/B6 mice received disposable total body irradiation for 7 days and were injected intraperitoneally with recombinant protein D1R or PBS to establish Notch signaling-activated mice (active group) and control mice (inactive group). We evaluated the intracorporal activity of D1R, the hematopoietic reconstruction, the cell cycle, and proliferation signal pathway of myeloid progenitor between the two groups. C57/B6 mice were randomly divided into the negative control group, D1R group, and positive control group. Mice in the D1R group and positive control group were given D1R and PBS intraperitoneally after equal dose of ionizing radiation, while mice in the negative control group were not treated. We detected the long-term toxicity after 3-month withdrawal of D1R. Results Compared with the non-knockout group, the survival status aggravated, the morphology of bone marrow hematopoietic stem/progenitor cells, bone marrow and peripheral blood nucleated cells, and myeloid cells was normal, but the number became less in the knockout group (all P＜0. 05). Correspondingly, D1R efficiently increased nuclear activation fragment NICD, suggesting the activation of Notch signaling in bone marrow hematopoietic cells. Compared with the inactive group, the number of bone marrow hematopoietic stem/progenitor cells, bone marrow and peripheral blood nucleated cells, and myeloid cells was higher (all P＜0. 05) , the proportion of myeloid precursor cells in the G0/G1 phase decreased, and increased in the S phase, respectively, and the expression of PI3K protein increased in the active group(all P < 0. 01). After 3-month withdrawal, there was no significant difference in cell morphology and hematopoietic lineage between the D1R group and negative control group, but the number of bone marrow hematopoietic stem/progenitor cells as well as bone marrow and peripheral blood myeloid cells was significantly higher than that of the positive control group (all P＜ 0. 05). Conclusion Notch signaling pathway can positively regulate the hematopoietic reconstitution after radiotherapy, especially myeloid remodeling. The mechanism may be that Notch signaling pathway activates PI3K proliferation signaling pathway in myeloid precursor cells and accelerates cell cycle progression.关键词
Notch信号途径/造血谱系重建/放射治疗/磷脂酰肌醇3-激酶/造血可塑性/小鼠Key words
Notch signaling pathway/hematopoietic lineage reconstruction/radiotherapy/PI3K/hematopoietic plasticity/mice分类
医药卫生引用本文复制引用
陈娟娟,周思朗,夏鸳鸯,赵永星,陈永乐,黄斯勇,吴必嘉..Notch信号途径对放疗后骨髓谱系造血重建的影响及其机制[J].山东医药,2018,58(8):26-30,5.基金项目
国家自然科学基金资助项目(81300397) （81300397）
广东省自然科学基金资助项目(2017A030310649). （2017A030310649）
