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首页> 外文期刊>Radiation and Environmental Biophysics >Administration of rat acute-phase protein α2-macroglobulin before total-body irradiation initiates cytoprotective mechanisms in the liver
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Administration of rat acute-phase protein α2-macroglobulin before total-body irradiation initiates cytoprotective mechanisms in the liver

机译：在全身照射启动肝脏中的细胞保护机制之前，给予大鼠急性期蛋白α2-巨球蛋白

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Previously, we showed that administration of the acute-phase protein α2-macroglobulin (α2M) to rats before total-body irradiation with 6.7 Gy (LD_(50/30)) of X-rays provides the same level of radioprotection as ami-fostine. Here, we compare the cytoprotective effects of α2M and amifostine on rat liver. The potential of the liver to replenish cells destroyed by ionizing radiation was assessed by immunoblot analysis with antibody to proliferating cell nuclear antigen (PCNA). After irradiation, in unprotected rats PCNA decreased 6-fold from the basal level. In rats pretreated with either α2M or amifostine, PCNA was increased throughout a 4 week follow-up period, indicating that hepatocyte proliferation was unaffected. Since PCNA is an important component of the repair machinery, its increased expression was accompanied by significantly lower DNA damage in α2M- and amifostine-treated rats. At 2 weeks after irradiation, the Comet assay revealed a 15-fold increase in DNA damage in unprotected rats, while in α2M- and amifostine-treated rats we observed 3- and 4-fold rise in damage, respectively. The improved protection to DNA damage was supported by elevated activity of the antioxidant systems. Compared to untreated rats, pretreatments with α2M and amifostine led to similar increases in levels of the inflammatory cytokine IL-6 and the redox-sensitive transcription factor NFκB, promoting upregulation of MnSOD, the major component of the cell's antioxidant axis, and subsequent increases in Mn/CuZnSOD and catalase enzymaticactivities. The results show that α2M induces protein factors whose interplay underlies radioprotection and support the idea that α2M is the central effector of natural radioprotection in the rat.
机译：先前，我们显示了在用6.7 Gy（LD_（50/30））的X射线全身照射之前，向大鼠施用急性期蛋白α2-巨球蛋白（α2M）可提供与阿米福司汀相同水平的放射防护。在这里，我们比较了α2M和氨磷汀对大鼠肝脏的细胞保护作用。通过用抗增殖细胞核抗原（PCNA）的抗体进行免疫印迹分析来评估肝脏补充被电离辐射破坏的细胞的潜力。辐照后，在未保护的大鼠中PCNA从基础水平降低了6倍。在用α2M或氨磷汀预处理的大鼠中，PCNA在整个4周的随访期内均升高，表明肝细胞增殖未受影响。由于PCNA是修复机制的重要组成部分，因此在α2M和氨磷汀治疗的大鼠中，PCNA的表达增加，而DNA损伤则明显降低。照射后2周，彗星试验显示，未保护的大鼠的DNA损伤增加了15倍，而用α2M和氨磷汀治疗的大鼠中，损伤分别增加了3倍和4倍。抗氧化剂系统活性的提高支持了对DNA损伤的更好保护。与未经治疗的大鼠相比，用α2M和氨磷汀进行的预处理导致炎性细胞因子IL-6和氧化还原敏感性转录因子NFκB的水平相似的升高，从而促进了MnSOD（细胞抗氧化剂轴的主要成分）的上调，并随后增加了Mn / CuZnSOD和过氧化氢酶的酶活性。结果表明，α2M诱导相互作用的蛋白质因子构成了放射防护的基础，并支持α2M是大鼠天然放射防护的主要效应器的观点。

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