文献类型：期刊文献

中文题名：黄芪多糖对X射线辐射所致BMSCs全基因组低甲基化的防护作用

英文题名：Protective Effect of Astragalus Polysaccharide on the Hypomethylation of BMSCs Genome Induced by Multiple X-ray Radiation

作者：李洋洋[1];王磊[2];张利英[1];张苡铭[1];何进鹏[3];周婷[1];周谷城[1];牛帆[1];刘永琦[1,4]

第一作者：李洋洋

机构：[1]甘肃中医药大学,甘肃省高校重大疾病分子医学与中医药防治研究省级重点实验室,兰州730000;[2]中国中医科学院西苑医院,北京100091;[3]甘肃省空间辐射生物学重点实验室,中国科学院近代物理研究所,兰州730000;[4]敦煌医学与转化教育部重点实验室,兰州730000

第一机构：甘肃中医药大学科研实验中心（甘肃省中医药标准化技术委员会秘书处）

年份：2022

卷号：39

期号：10

起止页码：1261

中文期刊名：中国现代应用药学

外文期刊名：Chinese Journal of Modern Applied Pharmacy

收录：CSTPCD;;北大核心:【北大核心2020】；CSCD:【CSCD2021_2022】；

基金：国家自然科学基金项目(81473457,81973595);甘肃省高等学校科研项目(2015A-095);西北中藏药协同创新中心项目(XBXT2015-1);甘肃省中医药研究中心开放基金项目(zyzx-2020-18);甘肃省高校重大疾病分子医学与中医药防治研究省级重点实验室开放基金项目(FZYX17-18-13);敦煌医学与转化教育部重点实验室开放基金项目(DHYX19-13)。

语种：中文

中文关键词：黄芪多糖;电离辐射;骨髓间充质干细胞;全基因组甲基化

外文关键词：Astragalus polysaccharide;ionizing radiation;bone marrow mesenchymal stem cells;whole genome methylation

摘要：目的研究黄芪多糖(Astragalus polysaccharide,APS)对多次X线电离辐射(ionizing radiation,IR)所致骨髓间充质干细胞(bone marrow stem cells,BMSCs)全基因组甲基化水平的影响。方法采用APS作用于5次每次2 Gy X射线辐射的BMSCs,将BMSCs分为对照组、APS组、IR组和APS+IR组。采用胞质分裂阻断法测定微核形成率;细胞染色体核型分析检测细胞核损伤;EPIGENTEK试剂盒检测各组BMSCs全基因组甲基化程度;Westernblotting检测各组BMSCs甲基转移酶DNMT3a、DNMT3b,甲基化CpG结合蛋白2(MeCP2)、甲基化CpG结合域蛋白2(MBD2)和各组BMSCs癌基因c-Myc、H-ras,抑癌基因P53、P16的蛋白表达水平。结果与对照组比较,IR组微核数目和染色体畸变明显增加(P<0.01),BMSCs全基因组甲基化程度明显降低(P<0.01);与IR组比较,APS+IR组微核数目和染色体畸变减少(P<0.05),BMSCs全基因组甲基化程度升高(P<0.01)。在蛋白表达上,与对照组比较,IR组DNMT3a和MeCP2均明显降低(P<0.01),c-Myc、H-ras的表达明显升高,P53、P16的表达显著降低(P<0.01);与IR组比较,APS+IR组DNMT3a和MeCP2明显升高(P<0.01或P<0.05),c-Myc、H-ras的表达降低(P<0.01),P53、P16的表达显著升高(P<0.01)。结论黄芪多糖能够防治多次X线辐射所致BMSCs全基因组甲基化水平,降低BMSCs的恶化风险。
OBJECTIVE To study the effect of Astragalus polysaccharide(APS) on the whole genome methylation level of bone marrow stem cells(BMSCs) induced by multiple X-ray ionizing radiation(IR).METHODS APS was used to act on BMSCs irradiated 5 times with 2 Gy X-rays per time,and BMSCs were divided into control group,APS group,IR group and APS+IR group.Cytokinesis blocking method was used to determine the rate of micronucleus formation;cell chromosome karyotype analysis was used to detect nuclear damage;EPIGENTEK kit was used to detect the degree of methylation of the whole genome of BMSCs in each group;Western blotting was used to detect the expression levels of BMSCs methyltransferase DNMT3a,DNMT3b,methyl-Cp G-binding protein 2(MeCP2),methyl-Cp G-binding domain protein 2(MBD2),oncogenes c-Myc,H-ras,and tumor suppressor genes P53 and P16 of BMSCs in each group.RESULTS Compared with the control group,the number of micronuclei and chromosome aberrations in IR group increased significantly(P<0.01),the degree of methylation of the whole genome of BMSCs in the IR group was significantly decreased(P<0.01);compared with IR group,the number of micronuclei and chromosome aberrations in the APS+IR group decreased(P<0.05),the degree of methylation of the whole genome of BMSCs in APS+IR group increased(P<0.01).In terms of protein characterization,compared with the control group,DNMT3a and MeCP2 in IR group were significantly decreased(P<0.01),the expressions of c-Myc and H-ras were significantly increased,and the expressions of P53 and P16 were significantly decreased(P<0.01).Compared with IR group,DNMT3a and MeCP2 in the APS+IR group were significantly increased(P<0.01 or P<0.05),the expressions of c-Myc and H-ras were decreased(P<0.01),and the expressions of P53 and P16 were significantly increased(P<0.01).CONCLUSION APS can prevent and control the methylation level of the whole genome of BMSCs induced by multiple X-ray radiation,and reduce the risk of deterioration of BMSCs.