当归多糖调控SIRT1/FOXO1通路抑制小鼠造血干细胞衰老

Role of SIRT1/FOXO1 pathway in inhibiting aging of mouse matopoietic stem cells by angelica polysaccharide

目的研究沉默信息调节因子1(SIRT1)/叉头转录因子1(FOXO1)通路在当归多糖(ASP)对抗小鼠造血干细胞(HSCs)衰老中的作用,探讨ASP抑制HSCs衰老的可能机制。方法C57BL/6J小鼠随机分为空白组、衰老组、ASP组;衰老组采用X线全身均匀照射,建立小鼠HSCs衰老模型;ASP组在照射期间给予200mg/kg ASP灌胃;对照组和衰老组给予等容量NS灌胃。免疫磁珠法分选HSCs,β-半乳糖苷酶(SA-β-Gal)染色检测衰老细胞、免疫荧光检测ROS含量、Western blot检测SIRT1及FOXO1表达。结果与空白组比较,衰老组HSCs SA-β-Gal染色阳性率及ROS产量增加(P<0.05);SIRT1与FOXO1表达减少(P<0.05)。与衰老组比较,ASP抑制小鼠衰老HSCs SA-β-Gal染色阳性率和ROS产量的增加(P<0.05);同时抑制SIRT1与FOXO1表达的减少(P<0.05)。结论ASP可能通过调控SIRT1/FOXO1通路抑制氧化应激延缓小鼠HSCs衰老。

Objective To study the role of silent information regulator 1(SIRT1)/forkhead transcription factor 1(FOXO1)pathway in the anti-aging effect of Angelica sinensis polysaccharide(ASP)on mouse hematopoietic stem cells(HSCs),and to explore the possible mechanism of ASP inhibiting HSCs aging.Methods C57BL/6J mice were randomly divided into blank group,aging group and ASP group.The aging group was irradiated with X-ray uniformly to establish the aging model of HSCs in mice.The ASP group was given 200mg/kg ASP during irradiation.The control group and aging group were given equal volume NS by gavage.Selecting HSCs by immunomagnetic beads,detecting aging cells by SA-β-Gal staining,detecting ROS content by immunofluorescence,and detecting SIRT1 and FOXO1 expression by Western blot.Results Compared with the blank group,the positive rate of HSCs SA-β-Gal staining and ROS production in aging group increased(P<0.05).The expression of SIRT1 and FOXO1 decreased(P<0.05).Compared with aging group,ASP inhibited the increase of positive rate of HSCs SA-β-Gal staining and ROS production in aging mice(P<0.05).Meanwhile,the expression of SIRT1 and FOXO1 was inhibited(P<0.05).Conclusion ASP may inhibit oxidative stress by regulating SIRT1/FOXO1 pathway and delay the aging of HSCs in mice.