食品科学 ›› 2023, Vol. 44 ›› Issue (21): 131-136.doi: 10.7506/spkx1002-6630-20221009-068

• 营养卫生 • 上一篇    

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

陈彩云, 王若宇, 张家乐, 张怡明, 石塔拉, 宓伟   

  1. (1.滨州医学院公共卫生与管理学院,山东 烟台 264003;2.滨州医学院第二临床医学院,山东 烟台 264003)
  • 发布日期:2023-12-13
  • 基金资助:
    国家自然科学基金青年科学基金项目(81302426;81902161);山东省高等学校科技计划项目(J17KA224); 山东省医药卫生科技发展计划项目(202212020325;202012020832)

Protective Effect of Solanum tuberosum Anthocyanin against Radiation-Induced Hematopoietic Stem/Progenitor Cell Senescence via the p53-p21Waf1/Cip1 Pathway

CHEN Caiyun, WANG Ruoyu, ZHANG Jiale, ZHANG Yiming, SHI Tala, MI Wei   

  1. (1. School of Public Health and Management, Binzhou Medical University, Yantai 264003, China;2. The Second Medical College, Binzhou Medical University, Yantai 264003, China)
  • Published:2023-12-13

摘要: 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。

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

Abstract: 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.

Key words: Solanum tuberosum anthocyanin; p53-p21Walf1/Cip1 pathway; radiation; hematopoietic stem/progenitor cell; senescence

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