| 王琪,赵珂,高雅萌,李欣,武云强,朱亚新,吕志春,孙慧颖,高慧英,向慎思,李长燕.电离辐射对小鼠造血干/祖细胞线粒体功能的影响[J].中华放射医学与防护杂志,2022,42(5):321-327 |
| 电离辐射对小鼠造血干/祖细胞线粒体功能的影响 |
| Effects of ionizing radiation on mitochondrial function of mouse hematopoietic stem and progenitor cells |
| 投稿时间：2022-02-22 |
| DOI：10.3760/cma.j.cn112271-20220222-00064 |
| 中文关键词: 造血干/祖细胞 线粒体 电离辐射 |
| 英文关键词:Hematopoietic stem and progenitor cells Mitochondria Ionizing radiation |
| 基金项目:国家自然科学基金面上项目(81770108);蛋白质组国家重点实验室自主课题(SKLP-K201802) |
| 作者 | 单位 | E-mail | | 王琪 | 安徽医科大学基础医学院, 合肥 230032 | | | 赵珂 | 中国人民解放军军事科学院军事医学研究院生命组学研究所, 北京 100850 | | | 高雅萌 | 安徽医科大学基础医学院, 合肥 230032 | | | 李欣 | 解放军第307临床学院(解放军总医院第五医学中心), 北京 100071 | | | 武云强 | 中国人民解放军军事科学院军事医学研究院生命组学研究所, 北京 100850 | | | 朱亚新 | 河北大学生命科学学院, 保定 071028 | | | 吕志春 | 中国人民解放军军事科学院军事医学研究院生命组学研究所, 北京 100850 | | | 孙慧颖 | 中国人民解放军军事科学院军事医学研究院生命组学研究所, 北京 100850 | | | 高慧英 | 中国人民解放军军事科学院军事医学研究院生命组学研究所, 北京 100850 | | | 向慎思 | 中国人民解放军军事科学院军事医学研究院生命组学研究所, 北京 100850 | | | 李长燕 | 安徽医科大学基础医学院, 合肥 230032 | fmmli@163.com |
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| 中文摘要: |
| 目的 研究不同剂量电离辐射对小鼠造血干/祖细胞(hematopoietic stem and progenitor cells, HSPCs)内线粒体功能的影响。方法 将48只C57BL/6小鼠按随机数表法分为对照组(0 Gy组)、全身60Co单次照射1.0 Gy组和4.5 Gy组,每组16只,照射后12、24 h检测HSPCs线粒体活性氧(ROS)水平、膜电位、线粒体数量及线粒体压力等。c-Kit+细胞体外接受60Co 单次15 Gy照射,24 h后检测线粒体功能。结果 建立小鼠造血系统辐射损伤模型,发现小鼠受不同剂量γ射线照射后24 h内外周血白细胞(t=12.41、18.31、16.48、14.16、19.08、20.25,P<0.05)、红细胞(t=4.81、6.62,P<0.05)及血小板(t=4.33、6.68,P<0.05)均明显减少,骨髓细胞集落形成能力下降(t=16.27、55.66、17.06、43.75,P<0.05),HSPCs数量降低(t=5.16、11.55,P<0.05),且呈现时间和剂量相关效应;1 Gy照射后,HSPCs中ROS水平差异无统计学意义(P>0.05),线粒体膜电位降低(t=8.82、9.24,P<0.05)、线粒体数量减少,且在照射后24 h,HSPCs线粒体功能、线粒体基础代谢指数增强(t= 7.36、3.68、4.58、3.15、3.15,P<0.05)。4.5 Gy照射后可引起HSPCs中ROS上升(t=4.63、4.12,P<0.05),线粒体数量降低,线粒体膜电位降低(t=12.29、10.46,P<0.05),最大呼吸能力和呼吸储备能力降低(t=7.81、5.78、6.70、5.83,P<0.05),12 h基础呼吸和氧化磷酸化ATP产能低(t=8.48、3.80,P<0.05),24 h 质子泄漏高(t=6.57,P<0.05),耦合效率低(t=11.43,P<0.05)。c-Kit+细胞经15 Gy照射后24 h,ROS水平显著上升(t=11.30,P<0.05),线粒体膜电位降低(t= 34.92,P<0.05),最大呼吸和呼吸储备能力提高(t=4.25、3.44,P<0.05)。结论 建立了HSPCs中系统评估线粒体功能方法,明确了电离辐射对HSPCs线粒体功能的影响,为深入揭示电离辐射致HSPCs线粒体损伤机制奠定基础。 |
| 英文摘要: |
| Objective To study the effect of different doses of 60Co γ-ray ionizing radiation on mitochondrial function in mouse hematopoietic stem and progenitor cells (HSPCs).Methods C57BL/6 mice were divided into control group, 1 Gy irradiation group and 4.5 Gy irradiation group. The mitochondrial functions were detected at 12 h and 24 h after irradiation, including ROS level, membrane potential, mitochondrial structure, and mitochondrial stress. Bone marrow c-Kit+ cells received a single 15 Gy irradiation in vitro, after 24 h, mitochondrial function was detected.Results It was found that mice leukocytes (t=12.41, 18.31, 16.48, 14.16, 19.08, 20.25, P<0.05), red blood cells (t=4.81, 6.62, P<0.05) and platelets (t=4.33, 6.68, P<0.05) were significantly reduced. The numbers of bone marrow colony formation unit (t=16.27, 55.66, 17.06, 43.75, P<0.05), and HSPCs (t=5.16, 11.55, P<0.05) were decreased dose-dependently post-irradiation. Under 1 Gy irradiation, the mitochondrial function and mitochondrial basal metabolic index of HSPCs (t= 7.36, 3.68, 4.58, 3.15, 3.15, P<0.05) were enhanced at 24 h post-irradiation. Under 4.5 Gy irradiation, mitochondrial number, mitochondrial membrane potential (t=12.29, 10.46, P<0.05), maximal respiration and spare respiratory capacity were decreased (t=7.81, 5.78, 6.70, 5.83, P<0.05), ROS level was increased (t=4.63, 4.12, P<0.05). The basal respiration and oxidative phosphorylated ATP production were reduced at 12 h after irradiation (t=8.48, 3.80, P<0.05); and the proton leakage was increased (t=6.57, P<0.05) and coupling efficiency was reduced (t=11.43, P<0.05) at 24 h after irradiation. In cultured c-Kit+ cells, the level of ROS (t=11.30, P<0.05) and the maximum respiration and spare respiratory capacity were increased (t=4.25, 3.44, P<0.05) while the mitochondrial membrane potential was decreased (t=34.92, P<0.05) significantly.Conclusions A method for systematically assessing mitochondrial function in HSPCs was established, and the effect of ionizing radiation on mitochondrial function of HSPCs was clarified, laying a foundation for further revealing the mechanism of ionizing radiation-induced mitochondrial damage in HSPCs. |
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