模拟太阳粒子事件对脑的生物效应研究

目的 通过模拟太阳粒子事件辐射,探究其脑损伤效应,为载人深空探测所致辐射健康风险评估提供依据。方法 根据太阳粒子事件主要特征,利用90 MeV的质子全身照射小鼠,照射剂量分别为0、0.1、0.3、0.5、1和2 Gy,照射后3、7 d,采用平衡木测试、转棒测试和新物体识别进行小鼠行为学检测,采用高尔基体染色和尼氏染色法检测海马树突棘密度和尼氏小体数量;采用WST-8法、TBA法和高压液相法检测脑组织超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量和神经递质含量;采用TUNEL法检测细胞凋亡;采用线性和线性平方拟合方法分析剂量与损伤指标变化的量效关系;根据所有脑损伤指标的显著变化的最小剂量点确定脑损伤阈值。结果 与对照组相比,1 Gy质子照射后3和7 d出现丝状伪足树突棘密度显著减小(t=1.82、2.30,P＜0.05)、CA1区异常尼氏小体显著增加(t=2.44、3.77,P＜0.05),照射后7 d即可出现DA含量显著增加(t=2.52,P＜0.05)、Glu含量显著增加(t=4.04,P＜0.05);2 Gy质子照射后3 d出现SOD活力下降(t=3.44,P＜0.05),照射后3、7 d出现MDA含量增加(t=1.90、2.14,P＜0.05)、转棒上攀爬时间减少(t=2.85、2.64,P＜0.05)、新物体识别倾向性下降(t=2.87、2.84,P＜0.05)、海马细胞凋亡增加(t=3.91、3.54,P＜0.05)、5-HT水平增加(t=2.81、2.69,P＜0.05),且在0.1~2 Gy剂量范围内具有剂量-效应关系(R²=0.74~0.99)。结论 90 MeV质子导致小鼠脑损伤的剂量阈值为1 Gy,获得14种量效关系模型,为短期深空飞行乘员的器官剂量限值制定和风险评估提供了生物学依据。

Biological effects of simulated solar particle events on brain

Objective To explore the produced-radiation brain damage in simulated solar particle events and to provide evidence for health risk assessment of radiation from manned deep space exploration. Methods According to the main characteristics of solar particle events, mice were treated with total body irradiation (TBI) with 90 MeV protons in a dose range from 0.1 to 2 Gy, with irradiation dose of 0, 0.1, 0.3, 0.5, 1, 2 Gy, respectively. At 3 and 7 d after irradiation, the behavior of mice was examined using balance beam tests, rotarod tests, and new object recognition tests. Then, the density of dendritic spines and the number of Nissl bodies in the hippocampus were measured using Golgi and Nissl staining. The superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and neurotransmitter content in brain tissue were detected using the WST-8 method, TBA method, and high pressure liquid chromatography (HPLC), respectively. Besides, cell apoptosis was determined using the TUNEL method, and the dose-response relationship, a function of dose change with damage index, was analyzed using linear and linear square fitting method. Finally, the minimum radiation dose causing a significant change in all indicators of brain damage was determined as the brain damage threshold. Results Compared to the control group, 1 Gy proton irradiation result ed in a significant decrease in the density of filopod dendritic spines (t=1.82, 2.30, P＜0.05) and a significant increase in abnormal Nissl bodies in the CA1 region (t=2.44, 3.77, P＜0.05). At 3 and 7 d after irradiation, as well as a significant increase in the DA (t=2.52, P＜0.05) and Glu contents (t=4.04, P＜0.05) on day 7. In contrast, 2 Gy proton irradiation result ed in a decrease in SOD activity on day 3 (t=3.44, P＜0.05), and an increase in the MDA content (t=1.90, 2.14, P＜0.05), hippocampal cell apoptosis (t = 3.91, 3.54, P < 0.05), and 5-HT levels (t=2.81, 2.69, P＜0.05), together with a decrease in climbing time in the rotarod tests (t=2.85, 2.64, P＜0.05) and propensity to recognize new objects (t=2.87, 2.84, P＜0.05) on days 3 and 7. Furthermore, a dose-response relationship was observed in the dose range from 0.1 to 2 Gy (R²=0.74-0.99). Conclusions The dose threshold of 90 MeV protons inducing brain damage in mice is inferred to be 1 Gy, and 14 dose-response models are developed, providing a biological basis for organ dose capping and risk assessment of crew experiencing short-term deep space flights.