低剂量氧离子和质子对雄性 C57BL/6J 小鼠心功能和结构的影响。
Effects of low-dose oxygen ions and protons on cardiac function and structure in male C57BL/6J mice.
机构信息
Division of Radiation Health, University of Arkansas for Medical Sciences, 4301 West Markham Slot 522-10, Little Rock, AR 72205, USA.
Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
出版信息
Life Sci Space Res (Amst). 2019 Feb;20:72-84. doi: 10.1016/j.lssr.2019.01.003. Epub 2019 Jan 15.
PURPOSE
Astronauts traveling beyond low-Earth orbit will be exposed to high linear-energy transfer charged particles. Because there is concern about the adverse effects of space radiation on the cardiovascular system, this study assessed cardiac function and structure and immune cell infiltration in a mouse model of charged-particle irradiation.
MATERIALS AND METHODS
Male C57BL/6 J mice were exposed to oxygen ions (O, 600 MeV/n at 0.25-0.26 Gy/min to a total dose of 0, 0.05, 0.1, 0.25, or 1 Gy), protons (150 MeV, 0.35-0.55 Gy/min to 0, 0.5, or 1 Gy), or protons (150 MeV, 0.5 Gy) followed by O (600 MeV/n, 0.1 Gy). Separate groups of mice received Cs γ-rays (1 Gy/min to 0, 0.5, 1, or 3 Gy) as a reference. Cardiac function and blood velocity were measured with ultrasonography at 3, 5, 7, and 9 months after irradiation. At 2 weeks, 3 months, and 9 months, cardiac tissue was collected to assess apoptosis, tissue remodeling, and markers of immune cells.
RESULTS
Ejection fraction and fractional shortening decreased at 3 and 7 months after O. These parameters did not change in mice exposed to γ-rays, protons, or protons followed by O. Each of the radiation exposures caused only small increases in cleaved caspase-3 and numbers of apoptotic nuclei. Changes in the levels of α-smooth muscle cell actin and a 75-kDa peptide of collagen type III in the left ventricle suggested tissue remodeling, but there was no significant change in total collagen deposition at 2 weeks, 3 months, and 9 months. Increases in protein amounts of cluster of differentiation (CD)2, CD68, and CD45 as measured with immunoblots at 2 weeks, 3 months, and 9 months after exposure to protons or O alone suggested immune cell infiltration. For type III collagen, CD2 and CD68, the efficacy in inducing protein abundance of CD2, CD68, and CD45 was O > protons > γ-rays > protons followed by O.
CONCLUSIONS
Low-dose, high-energy charged-particle irradiation caused mild changes in cardiac function and tissue remodeling in the mouse.
目的
宇航员在低地球轨道以外的飞行中会暴露于具有高线性能量转移的带电粒子。由于人们担心空间辐射对心血管系统的不良影响，因此本研究评估了荷电粒子辐照的小鼠模型中的心脏功能和结构以及免疫细胞浸润。
材料和方法
雄性 C57BL/6J 小鼠接受氧离子（O，600 MeV/n，0.25-0.26Gy/min，总剂量为 0、0.05、0.1、0.25 或 1Gy）、质子（150 MeV，0.35-0.55Gy/min，0、0.5 或 1Gy）或质子（150 MeV，0.5Gy）照射后再接受 O（600 MeV/n，0.1Gy）照射。单独的小鼠组接受 Csγ射线（1Gy/min，0、0.5、1 或 3Gy）作为参考。在照射后 3、5、7 和 9 个月，使用超声心动图测量心功能和血流速度。在 2 周、3 个月和 9 个月时，采集心脏组织以评估细胞凋亡、组织重塑和免疫细胞标志物。
结果
O 照射后 3 个月和 7 个月时，射血分数和短轴缩短率降低。γ 射线、质子或质子照射后 O 照射的小鼠心功能参数没有变化。每种辐射照射仅导致小幅度增加的 cleaved caspase-3 和凋亡核数量。左心室中α-平滑肌肌动蛋白和 III 型胶原的 75kDa 肽的水平变化表明组织重塑，但在 2 周、3 个月和 9 个月时总胶原沉积没有显著变化。暴露于质子或 O 后 2 周、3 个月和 9 个月，用免疫印迹法测量的分化群（CD）2、CD68 和 CD45 的蛋白量增加表明免疫细胞浸润。对于 III 型胶原、CD2 和 CD68，诱导 CD2、CD68 和 CD45 蛋白丰度的功效为 O＞质子＞γ 射线＞质子照射后 O。
结论
低剂量高能荷电粒子辐照导致小鼠心脏功能和组织重塑发生轻微变化。
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