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Angelica Sinensis Polysaccharide Prevents Hematopoietic Stem Cells Senescence in D-Galactose-Induced Aging Mouse Model

机译:当归多糖预防D-半乳糖诱导的衰老小鼠模型中造血干细胞衰老

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摘要

Age-related regression in hematopoietic stem/progenitor cells (HSC/HPCs) limits replenishment of the blood and immune system and hence contributes to hematopoietic diseases and declined immunity. In this study, we employed D-gal-induced aging mouse model and observed the antiaging effects of Angelica Sinensis Polysaccharide (ASP), a major active ingredient in dong quai (Chinese Angelica Sinensis), on the Sca-1+ HSC/HPCs in vivo. ASP treatment prevents HSC/HPCs senescence with decreased AGEs levels in the serum, reduced SA-β-Gal positive cells, and promoted CFU-Mix formation in the D-gal administrated mouse. We further found that multiple mechanisms were involved: (1) ASP treatment prevented oxidative damage as total antioxidant capacity was increased and levels of reactive oxygen species (ROS), 8-OHdG, and 4-HNE were declined, (2) ASP reduced the expression of γ-H2A.X which is a DNA double strand breaks (DSBs) marker and decreased the subsequent ectopic expressions of effectors in p16Ink4a-RB and p19Arf-p21Cip1/Waf senescent pathways, and (3) ASP inhibited the excessive activation of Wnt/β-catenin signaling in aged HSC/HPCs, as the expressions of β-catenin, phospho-GSK-3β, and TCF-4 were decreased, and the cyto-nuclear translocation of β-catenin was inhibited. Moreover, compared with the positive control of Vitamin E, ASP exhibited a better antiaging effect and a weaker antioxidation ability, suggesting a novel protective role of ASP in the hematopoietic system.
机译:造血干/祖细胞(HSC / HPC)中与年龄相关的退化限制了血液和免疫系统的补充,因此导致造血疾病和免疫力下降。在这项研究中,我们采用D-gal诱导的衰老小鼠模型,观察当归主要活性成分当归多糖(ASP)对Sca-1 + < / sup>体内的HSC / HPC。 ASP处理可防止HSC / HPC衰老,并降低血清AGEs水平,减少SA-β-Gal阳性细胞并促进D-gal给药小鼠的CFU-Mix形成。我们进一步发现涉及多种机制:(1)ASP处理可防止氧化损伤,因为总抗氧化剂容量增加,活性氧(ROS),8-OHdG和4-HNE的水平下降,(2)ASP降低了氧化损伤。 DNA双链断裂(DSBs)标记γ-H2A.X的表达并降低p16 Ink4a -RB和p19 Arf -p21中效应子的随后异位表达 Cip1 / Waf 衰老途径,(3)ASP抑制了衰老的HSC / HPC中Wnt /β-catenin信号的过度激活,其表达方式包括β-catenin,phospho-GSK-3β和TCF-4降低,β-catenin的细胞核易位受到抑制。此外,与维生素E的阳性对照相比,ASP表现出更好的抗衰老作用和较弱的抗氧化能力,表明ASP在造血系统中具有新型的保护作用。

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