首页|紫薯花青素通过调节p53-p21Waf1/Cip1信号通路对辐射致造血干/祖细胞衰老的保护作用

紫薯花青素通过调节p53-p21Waf1/Cip1信号通路对辐射致造血干/祖细胞衰老的保护作用

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  • 国家科技期刊平台
  • NETL
  • NSTL
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目的:探讨紫薯花青素(Solanum tuberosum anthocyanin,STA)对辐射致造血干细胞(hematopoietic stem cell,HSC)/造血祖细胞(hematopoietic progenitor cell,HPC)衰老起保护作用的分子机制.方法:将C57BL/6小鼠随机分为对照组、模型组、STA治疗组和STA预防组,利用X射线照射构建衰老细胞模型.给药后用血细胞分析仪检测各组小鼠血液指标;免疫磁性分选法分离纯化各组小鼠Sca-1+HSC/HPC,并用衰老相关β-半乳糖苷酶(senescence-associated β-galactosidase,SA-β-Gal)染色试剂盒对其进行染色实验并计算各组阳性率;利用HSC/HPC混合集落(colony forming unit-mixture,CFU-Mix)数评价各组细胞形成HSC/HPC集落能力与分化潜能;流式细胞术分析细胞周期;实时定量聚合酶链反应(quantitative real-time polymerase chain reaction,qPCR)检测p53和p21Waf1/Cip1 mRNA的表达;Western blot检测p53和p21Waf1/Cip1蛋白的表达.结果:与对照组相比,模型组小鼠外周血指标红细胞、白细胞、血小板数均极显著降低(P＜0.01),衰老细胞阳性率极显著增加(P＜0.01),Sca-1+HSC/HPC形成CFU-Mix的数量极显著减少(P＜0.01),G0/G1期比例极显著升高(P＜0.01),G2/M和S期比例极显著降低(P＜0.01),p53和p21Waf1/Cip1 mRNA和蛋白的相对表达量极显著增加(P＜0.01),STA治疗和STA预防均可分别显著和极显著恢复模型组小鼠以上指标,其中STA预防效果更好.结论:STA可以通过调节p53-p21Waf1/Cip1信号通路保护受到辐射的HSC/HPC.
Protective Effect of Solanum tuberosum Anthocyanin against Radiation-Induced Hematopoietic Stem/Progenitor Cell Senescence via the p53-p21Waf1/Cip1 Pathway
Objective:To investigate the molecular mechanism underlying the protective effect of Solanum tuberosum anthocyanin(STA)on radiation-induced hematopoietic stem/progenitor cell senescence.Methods:C57BL/6 mice were randomly divided into three groups:control,model,STA treatment and STA prevention,and the cell senescence model was constructed by X-ray irradiation.The hemogram of mice in each group were examined using a hematology analyzer after drug administration.Stem cell antigen 1 positive hematopoietic stem/progenitor cells(Sca-1+HSC/HPCs)were isolated and purified from each group by immunomagnetic cell sorting and were stained using a senescence-associated β-galactosidase(SA-β-Gal)kit to calculate the proportion of SA-β-Gal positive cells.The number of mixed lineage colony forming unit(CFU-Mix)was used to evaluate the colony-forming capacity and differentiation potential of hematopoietic stem/progenitor cells.Cell cycle was analyzed by flow cytometry.The mRNA and protein expression of p53 and p21Waf1/Cip1 were detected by quantitative real-time polymerase chain reaction(qPCR)and Western blot.Results:The numbers of red blood cells(RBCs),white blood cells(WBCs)and platelets in the peripheral blood were significantly lower in the model group than in the control group(P<0.01).In addition,compared with the control group,the proportion of SA-β-Gal positive cells significantly increased(P<0.01),the number of CFU-Mix significantly fell(P<0.01),the proportion of G0/G1 phase cells significantly increased,the proportions of G2/M and S phase cells significantly dropped(P<0.01),and the relative mRNA and protein expression levels of p53 and p21Waf1/Cip1 significantly increased in the model group(P<0.01).STA could significantly restore the above parameters of mice in the model group irrespective of whether it was administered before or after X-ray radiation,with more pronounced effect being observed in the former case.Conclusion:STA can protect hematopoietic stem/progenitor cells against radiation by regulating the p53-p21Waf1/Cip1 pathway.

Solanum tuberosum anthocyaninp53-p21Walf1/Cip1 pathwayradiationhematopoietic stem/progenitor cellsenescence

陈彩云、王若宇、张家乐、张怡明、石塔拉、宓伟

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滨州医学院公共卫生与管理学院,山东 烟台 264003

滨州医学院第二临床医学院,山东 烟台 264003

紫薯花青素 p53-p21Waf1/Cip1信号通路 辐射 造血干/祖细胞 衰老

国家自然科学基金青年科学基金国家自然科学基金青年科学基金山东省高等学校科技计划项目山东省医药卫生科技发展计划项目山东省医药卫生科技发展计划项目

8130242681902161J17KA224202212020325202012020832

2023

10.7506/spkx1002-6630-20221009-068

食品科学
北京食品科学研究院

食品科学

CSTPCDCSCD北大核心
影响因子：1.327
ISSN：1002-6630
年,卷(期)：2023.44(21)
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