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Effects of single-dose protons or oxygen ions on function and structure of the cardiovascular system in male Long Evans rats.
Life Sciences in Space Research ( IF 2.5 ) Pub Date : 2020-05-22 , DOI: 10.1016/j.lssr.2020.04.002
Vijayalakshmi Sridharan 1 , John W Seawright 2 , Reid D Landes 3 , Maohua Cao 4 , Preeti Singh 1 , Catherine M Davis 5 , Xiao-Wen Mao 6 , Sharda P Singh 7 , Xin Zhang 8 , Gregory A Nelson 6 , Marjan Boerma 1
Affiliation  

Purpose

Studies are required to determine whether exposures to radiation encountered during manned missions in deep space may have adverse effects on the cardiovascular system. Most of the prior studies on effects of simulated space radiation on the heart and vasculature have been performed in mouse models. To provide data from a second animal species, two studies were performed to assess effects of high-energy charged particle radiation on the heart and abdominal aorta in a rat model.

Materials and methods

In study A, male Long Evans rats were exposed to whole-body protons (250 MeV, 0.5 Gy) or oxygen ions (16O, 600 MeV/n, 0.5 Gy), and ultrasonography was used to measure in vivo cardiac function and blood flow parameters at 3, 5, 9 and 12 months after radiation, followed by tissue collection at 12 months. In study B, male Long Evans rats were exposed to 16O (1 GeV/n, 0.01-0.25 Gy), and hearts collected at 6 to 7 and 12 months for histology and western-blots.

Results

Both protons (250 MeV) and 16O (600 MeV/n) caused a decrease in left ventricular posterior wall thickness at 3-5 months, but did not change echocardiographic measures of cardiac function. In Pulsed-wave Doppler assessment of the abdominal aorta, an increase was seen in mean velocity, peak velocity, and velocity time integral at 12 months after 16O (600 MeV/n), suggesting a change in vascular function. There were no significant changes in histopathology or histological quantification of total collagens in heart or aorta. On the other hand, an increase was seen in a 75 kDa peptide of collagen type III in the left ventricle of rats exposed to protons (250 MeV) and 16O (600 MeV/n and 1 GeV/n), suggesting that radiation caused remodeling of existing collagens in the heart. 16O (600 MeV/n and 1 GeV/n) caused increases in left ventricular protein levels of immune cell markers CD2, CD4, CD8, and CD68.

Conclusion

A single low dose of whole body protons or 16O in male Long Evans rats did not change cardiac function or induce gross pathological changes in the heart or aorta, but induced mild changes in vascular function and remodeling of existing collagens in the heart. Altogether, studies in prior mouse models and the current work in rats indicate minor changes in cardiac function and structure after a low dose of single-ion radiation.



中文翻译:

单剂量质子或氧离子对雄性 Long Evans 大鼠心血管系统功能和结构的影响。

目的

需要进行研究以确定在深空载人任务期间遇到的辐射暴露是否可能对心血管系统产生不利影响。大多数先前关于模拟空间辐射对心脏和脉管系统影响的研究都是在小鼠模型中进行的。为了提供来自第二种动物物种的数据,进行了两项研究以评估高能带电粒子辐射对大鼠模型中心脏和腹主动脉的影响。

材料和方法

在研究 A 中,雄性 Long Evans 大鼠暴露于全身质子 (250 MeV, 0.5 Gy) 或氧离子 ( 16 O, 600 MeV/n, 0.5 Gy),并使用超声测量体内心脏功能和血液放射后 3、5、9 和 12 个月的血流参数,然后在 12 个月时收集组织。在研究 B 中,雄性 Long Evans 大鼠暴露于16 O(1 GeV/n,0.01-0.25 Gy),并在 6 至 7 个月和 12 个月时收集心脏用于组织学和蛋白质印迹。

结果

质子 (250 MeV) 和16 O (600 MeV/n) 在 3-5 个月时均导致左心室后壁厚度减少,但未改变心脏功能的超声心动图测量值。在腹主动脉的脉冲波多普勒评估中,在16 O (600 MeV/n)后 12 个月,平均速度、峰值速度和速度时间积分增加,表明血管功能发生了变化。心脏或主动脉中总胶原的组织病理学或组织学量化没有显着变化。另一方面,在暴露于质子 (250 MeV) 和16O(600 MeV/n 和 1 GeV/n),表明辐射导致心脏中现有胶原蛋白的重塑。16 O(600 MeV/n 和 1 GeV/n)导致免疫细胞标志物 CD2、CD4、CD8 和 CD68 的左心室蛋白水平增加。

结论

在雄性 Long Evans 大鼠中,单次低剂量的全身质子或16 O 不会改变心脏功能或引起心脏或主动脉的严重病理变化,但会引起血管功能的轻微变化和心脏现有胶原蛋白的重塑。总之,对先前小鼠模型的研究和目前在大鼠中的研究表明,在低剂量的单离子辐射后,心脏功能和结构发生了微小的变化。

更新日期:2020-05-22
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