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β-D-葡聚糖对高传能线密度碳离子辐照小鼠的辐射防护作用机制。

The mechanisms for the radioprotective effect of beta-d-glucan on high linear-energy-transfer carbon ion irradiated mice.

机构信息

Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; University of Chinese Academy of Sciences, Beijing 100049, China.

Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.

出版信息

Int J Biol Macromol. 2019 Jun 15;131:282-292. doi: 10.1016/j.ijbiomac.2019.03.073. Epub 2019 Mar 12.

DOI:10.1016/j.ijbiomac.2019.03.073
PMID:30876896
Abstract

S. cerevisiae-derived-beta-d-glucan (S. cerevisiae-BG) is a natural polysaccharide with various biological effects. The present study was to investigate the protective effect of S. cerevisiae-BG on the injury induced by high linear-energy-transfer (LET) carbon ion irradiation and to reveal the protective mechanisms. Female mice were orally administrated with S. cerevisiae-BG before irradiation. 30-day survival of 6 Gy irradiated-mice was monitored. The damage and recovery of hematopoietic system were evaluated after 2 Gy irradiation, cytokines in plasma were detected, transcriptomics of bone marrow mononuclear cells (BMMNCs) were detected and analyzed. The mortality results showed that S. cerevisiae-BG could prolong the survival of mice exposed to 6 Gy. The results of BMMNCs injury analysis showed that S. cerevisiae-BG could reduce the ROS level, mitigate DNA damage and apoptosis. S. cerevisiae-BG increased the plasma radioprotective cytokines level in irradiated mice. Transcriptomics analysis revealed that S. cerevisiae-BG modulated the gene expression in BMMNCs of irradiated mice, 256 genes were significantly up-regulated and 97 genes were significantly down-regulated. Gene function and Gene Ontology analysis indicated the key genes related to hematopoiesis and immunity. Pathway analysis revealed that these up-regulated genes mainly focus on PI3K-Akt pathway and down-regulated genes mainly focus on MAPK pathway. These data contribute to understanding the molecular mechanisms of the radioprotective effect of S. cerevisiae-BG.

摘要

酿酒酵母来源的β-葡聚糖(S. cerevisiae-BG)是一种具有多种生物学效应的天然多糖。本研究旨在探讨 S. cerevisiae-BG 对高传能线密度(LET)碳离子照射诱导损伤的保护作用,并揭示其保护机制。雌性小鼠在照射前经口给予 S. cerevisiae-BG。监测 6 Gy 照射后 30 天的小鼠存活率。在 2 Gy 照射后评估造血系统的损伤和恢复情况,检测血浆中的细胞因子,检测和分析骨髓单个核细胞(BMMNCs)的转录组。死亡率结果表明,S. cerevisiae-BG 可延长 6 Gy 暴露小鼠的存活时间。BMMNCs 损伤分析结果表明,S. cerevisiae-BG 可降低 ROS 水平,减轻 DNA 损伤和细胞凋亡。S. cerevisiae-BG 增加了照射后小鼠血浆中的辐射保护细胞因子水平。转录组分析显示,S. cerevisiae-BG 调节了照射后小鼠 BMMNCs 的基因表达,256 个基因显著上调,97 个基因显著下调。基因功能和基因本体论分析表明,这些与造血和免疫相关的关键基因。通路分析表明,这些上调的基因主要集中在 PI3K-Akt 通路,而下调的基因主要集中在 MAPK 通路。这些数据有助于理解 S. cerevisiae-BG 辐射保护作用的分子机制。

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