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SIRT5缺失对小鼠造血干细胞损伤恢复的影响

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目的:探讨在5-FU诱导下脱酰基酶Sirtuin 5对小鼠造血干细胞损伤恢复的影响.方法:采用流式细胞术分析SIRT5缺失对小鼠造血干/祖细胞比例,胸腺T细胞的发育情况,外周血和脾脏中T细胞、B细胞和髓系细胞比例的影响.使用5-FU进行化疗损伤诱导,采用流式细胞术分析SIRT5缺失对骨髓造血干/祖细胞比例的影响,同时检测SIRT5缺失小鼠造血干/祖细胞的细胞周期和凋亡.通过流式分选进行造血干细胞体外培养,分析SIRT5缺失对造血干细胞增殖能力的影响.结果:与野生型相比,SIRT5的缺失不影响小鼠胸腺中T细胞的发育以及外周血和脾脏中T细胞、B细胞和髓系细胞比例.在骨髓中,SIRT5缺失小鼠的造血干/祖细胞比例升高.在5-FU处理的造血损伤情况下,SIRT5缺失会导致小鼠造血干细胞比例下降(P<0.05),并且SIRT5缺失小鼠的造血干/祖细胞由G0期向G1期激活(P<0.05),同时伴随早期凋亡率显著升高(P<0.05).通过体外单克隆培养,与野生型相比,SIRT5缺失小鼠的造血干细胞克隆形成能力显著下降(P<0.05).结论:SIRT5缺失导致造血干细胞体外克隆能力下降.在造血应激情况下,SIRT5缺失不利于小鼠造血干/祖细胞损伤后的恢复.
The Effect of SIRT5 Deletion on Recovery of Hematopoietic Stem Cells after Injury in Mouse
Objective:To investigate the effect of deacylase Sirtuin 5 in the recovery of hematopoietic stem cells(HSCs)after treated by 5-FU in mouse.Methods:Flow cytometry was used to analyze the effect of SIRT5 deletion on the proportion of hematopoietic stem/progenitor cells(HSPCs)in bone marrow(BM),the proportion of T cells,B cells and myeloid cells(TBM)in peripheral blood(PB)and spleen,and the development of T cells in thymus.Mouse were treated with 5-FU to study the effect of SIRT5 deletion on the cell cycle,apoptosis and the proportion of HSPCs in BM.The effect of SIRT5 deletion on the proliferation of HSCs was analyzed by flow sorting in vitro.Results:SIRT5 deletion did not affect the development of T cells in thymus and the proportion of TBM cells in PB and spleen compared with wild type mice.SIRT5 deletion increased proportion of HSPCs in BM.After 5-FU treatment,the proportion of HSCs in SIRT5 deletion mice was significant decreased(P<0.05),the HSPC in SIRT5 deletion mice was activated from G0 to G1 phase(P<0.05),and the proportion of early apoptosis increased(P<0.05).By monoclonal culture in vitro,the ability of HSCs to form clones in SIRT5 deletion mice was decreased significantly(P<0.05).Conclusion:SIRT5 deletion lead to a decreased the ability of HSCs to clone in vitro.SIRT5 deletion is not conducive to the recovery of HSPCs injury in mice under hematopoietic stress.

SIRT5hematopoietic stem cell5-Fluorouracil

邓远遥、牟汉川、张弦、任帆、陈陟阳、鞠振宇、楼慧玲

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暨南大学衰老与再生医学研究院,广东广州 510632

广州市第一人民医院老年病科,广东广州 510180

SIRT5 造血干细胞 5-氟尿嘧啶

国家重点研发计划国家自然科学基金

2021YFA110010392049112

2024

中国实验血液学杂志
中国病理生理学会

中国实验血液学杂志

CSTPCD北大核心
影响因子:0.988
ISSN:1009-2137
年,卷(期):2024.32(2)
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