人参皂苷 Rg1 增强了造血干/祖细胞对小鼠辐射诱导衰老的抵抗力。
Ginsenoside Rg1 enhances the resistance of hematopoietic stem/progenitor cells to radiation-induced aging in mice.
机构信息
Laboratory of Stem Cells and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, China.
Department of Histology and Embryology, Dali University, Dali 671000, China.
出版信息
Acta Pharmacol Sin. 2014 Jan;35(1):143-50. doi: 10.1038/aps.2013.136. Epub 2013 Dec 16.
AIM
To investigate the effects of ginsenoside Rg1 on the radiation-induced aging of hematopoietic stem/progenitor cells (HSC/HPCs) in mice and the underlying mechanisms.
METHODS
Male C57BL/6 mice were treated with ginsenoside Rg1 (20 mg·kg(-1)·d(-1), ip) or normal saline (NS) for 7 d, followed by exposure to 6.5 Gy X-ray total body irradiation. A sham-irradiated group was treated with NS but without irradiation. Sca-1(+) HSC/HPCs were isolated and purified from their bone marrow using MACS. DNA damage was detected on d 1. The changes of anti-oxidative activities, senescence-related markers senescence-associated β-galactosidase (SA-β-gal) and mixed colony-forming unit (CFU-mix), P16(INK4a) and P21(Cip1/Waf1) expression on d 7, and cell cycle were examined on d 1, d 3, and d 7.
RESULTS
The irradiation caused dramatic reduction in the number of Sca-1(+) HSC/HPCs on d 1 and the number barely recovered until d 7 compared to the sham-irradiated group. The irradiation significantly decreased SOD activity, increased MDA contents and caused DNA damage in Sca-1(+) HSC/HPCs. Moreover, the irradiation significantly increased SA-β-gal staining, reduced CFU-mix forming, increased the expression of P16(INK4a) and P21(Cip1/Waf1) in the core positions of the cellular senescence signaling pathways and caused G1 phase arrest of Sca-1(+) HSC/HPCs. Administration of ginsenoside Rg1 caused small, but significant recovery in the number of Sca-1(+) HSC/HPCs on d 3 and d 7. Furthermore, ginsenoside Rg1 significantly attenuated all the irradiation-induced changes in Sca-1(+) HSC/HPCs, including oxidative stress reaction, DNA damage, senescence-related markers and cellular senescence signaling pathways and cell cycle, etc.
CONCLUSION
Administration of ginsenoside Rg1 enhances the resistance of HSC/HPCs to ionizing radiation-induced senescence in mice by inhibiting the oxidative stress reaction, reducing DNA damage, and regulating the cell cycle.
目的
探讨人参皂苷 Rg1 对小鼠造血干/祖细胞（HSC/HPC）辐射衰老的影响及其机制。
方法
雄性 C57BL/6 小鼠用人参皂苷 Rg1（20 mg·kg（-1）·d（-1），ip）或生理盐水（NS）处理 7 d，然后接受 6.5 Gy 全身 X 射线照射。假照射组用 NS 处理但不照射。用 MACS 从骨髓中分离和纯化 Sca-1（+）HSC/HPC。在第 1 天检测 DNA 损伤。在第 7 天检测抗氧化活性、衰老相关标志物衰老相关β-半乳糖苷酶（SA-β-gal）和混合集落形成单位（CFU-mix）、P16（INK4a）和 P21（Cip1/Waf1）的变化，以及细胞周期在第 1、3 和 7 天进行检测。
结果
照射导致第 1 天 Sca-1（+）HSC/HPC 数量明显减少，与假照射组相比，第 7 天数量几乎没有恢复。照射显著降低 SOD 活性，增加 MDA 含量，导致 Sca-1（+）HSC/HPC 中的 DNA 损伤。此外，照射显著增加 SA-β-gal 染色，减少 CFU-mix 形成，增加细胞衰老信号通路核心部位的 P16（INK4a）和 P21（Cip1/Waf1）的表达，并导致 Sca-1（+）HSC/HPC 的 G1 期停滞。人参皂苷 Rg1 处理可使第 3 天和第 7 天 Sca-1（+）HSC/HPC 的数量略有但显著恢复。此外，人参皂苷 Rg1 显著减轻了照射对 Sca-1（+）HSC/HPC 的所有变化，包括氧化应激反应、DNA 损伤、衰老相关标志物和细胞衰老信号通路以及细胞周期等。
结论
人参皂苷 Rg1 通过抑制氧化应激反应、减少 DNA 损伤和调节细胞周期，增强了 HSC/HPC 对小鼠电离辐射诱导衰老的抵抗力。
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