Alteration of Metal Elements in Radiation Injury: Radiation-Induced Copper Accumulation Aggravates Intestinal Damage
Alteration of Metal Elements in Radiation Injury: Radiation-Induced Copper Accumulation Aggravates Intestinal Damage
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辐射损伤中金属元素的变化：辐射引起的铜积累加剧肠道损伤
DOI：
10.1177/1559325820904547
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发表时间：
2020
期刊：
影响因子：
2.5
通讯作者：
Shuyu Zhang
中科院分区：
文献类型：
--
作者：
Li Zhong;Aijing Dong;Yang Feng;Xi Wang;Yiying Gao;Yuji Xiao;Ji Zhang;Dan He;Jianping Cao;Wei Zhu;Shuyu Zhang
电离辐射对多种组织造成损害，特别是对辐射敏感的组织，如小肠。辐射引起的损伤主要是由体内氧化应激增加引起的。研究表明，微量金属元素在人体氧化应激中发挥着不可替代的作用，可能与辐射引起的组织损伤有关。然而，微量金属元素在放射损伤中的变化及其功能意义尚不清楚。本研究在小鼠模型中探讨了7种微量金属元素与辐射损伤的关系。我们发现，在小鼠血清中的锌和铜的浓度显着降低照射后，而镍，锰，钒，钴，锡的电感耦合等离子体质谱法没有改变。详细描述了铜在辐射诱导的肠道中的作用。照射后小肠铜含量增加，心脏铜含量降低。免疫组织化学染色显示，铜转运蛋白copper transport 1在辐射小鼠小肠中表达上调，提示其可能参与辐射诱导的铜蓄积。在细胞水平上，CuCl 2的加入增强了放射诱导的活性氧在人小肠上皮细胞和IEC-6细胞中的表达。此外，受损细胞中铜的水平可能与辐射诱导的损伤的严重程度有关，如细胞活力测定所证明的。这些结果表明，铜可能参与辐射诱导的组织损伤的进展，并可能是一个潜在的治疗靶点。
Ionizing radiation causes damage to a variety of tissues, especially radiation-sensitive tissues, such as the small intestine. Radiation-induced damage is caused primarily by increased oxidative stress in the body. Studies have shown that trace metal elements play an irreplaceable role in oxidative stress in humans, which may be associated with radiation-induced tissue damage. However, the alteration and functional significance of trace metal elements in radiation-induced injury is not clear. In this study, we explored the association between radiation-induced damage and 7 trace metal elements in mouse models. We found that the concentration of zinc and copper in mice serum was decreased significantly after irradiation, whereas that of nickel, manganese, vanadium, cobalt, and stannum was not changed by inductively coupled plasma mass spectrometry. The role of copper in radiation-induced intestines was characterized in detail. The concentration of copper was increased in irradiated intestine but reduced in irradiated heart. Immunohistochemistry staining showed that copper transporter protein copper transport 1 expression was upregulated in irradiated mouse intestine, suggesting its potential involvement in radiation-induced copper accumulation. At the cellular level, the addition of CuCl2 potentiated radiation-induced reactive oxygen species in intestine-derived human intestinal epithelial cell and IEC-6 cells. Moreover, the level of copper in damaged cells may be related to the severity of radiation-induced damage as evidenced by a cell viability assay. These results indicate that copper may be involved in the progression of radiation-induced tissue damage and may be a potential therapeutic target.