中文摘要：

目的：探讨去乙酰化酶1（SIRT1）在人参皂苷Rg1体内正向调控造血干/祖细胞（HSC/HPC）衰老中的作用。方法：免疫磁性分选法分离纯化雄性供体小鼠Sca-1^＋HSC/HPC连续移植3代构建HSC/HPC衰老体内模型。^60Co γ射线致死剂量辐射雌性受体鼠后分4组，照射对照组、衰老模型组、Rg1治疗衰老组和Rg1预防衰老组。衰老相关β半乳糖苷酶（SA-β-Gal）染色、造血祖细胞混合集落（CFU-Mix）培养和细胞周期分析检测Rg1体内调控Sca-1^＋HSC/HPC衰老的作用。荧光定量PCR及免疫印迹检测衰老调控分子SIRT1、核因子-κB（NF-κB）mRNA及蛋白的表达。结果：连续移植后受体鼠Sca-1^＋HSC/HPC出现细胞衰老特征，随移植代数的增加，Sca-1^＋HSC/HPC G0/G1期细胞比例及SA-β-Gal染色阳性率增高，CFU-Mix数量下降。与同代衰老模型组相比，Rg1治疗衰老组及Rg1预防衰老组受体鼠Sca-1^＋HSC/HPC G0/G1期细胞比例、SA-β-Gal染色阳性率下降，CFU-Mix数量升高；SIRT6 mRNA及蛋白表达上调，NF-κB mRNA及蛋白表达下调；Rg1预防衰老组各指标变化均较Rg1治疗衰老组明显。结论：Rg1可能通过调控SIRT1/NF-κB信号轴发挥其在连续移植过程中抗Sca-1^＋HSC/HPC衰老的作用。

英文摘要：

Objective： To investigate effects of sirtuin 1 （SIRT1） in positive regulation of ginsenoside Rgl on hematopoietic stem cell and progenitor cell senescence in vivo. Methods： Sca-1^＋ HSC/HPC from male donator mouse was isolated and purified by magnetic activated cell sorting（MACS）. Sca-1^＋ HSC/HPC replicability aged model in vivo was established through the Sca-1^＋ HSC/HPC serial transplantation. Female recipient mice radiated lethal dose from ^60Coγ ray were divided into four groups： control group, aged model, Rgl treat aging group and Rg1 prevent aging group. The effect of Rg1 to delay Sca-1^＋ HSC/HPC senencence in vivo were evaluated by senescence-associated β-galactosidase （SA-β-gal） staining, mixed hematopoietic progenitor cell culture（CFU-Mix） and cell cycle assay. The expressions of SIRT1 and nuclear factor-κB（NF-κB） mRNA and protein were detected by quantitative PCR and Western blotting. Results： With the increase of transplantation, Sca-1^＋ HSC/HPC showed aging character： the number of cells entered G0/G1 phase and the percentage of SA-β-gal positive cells were increased; the number of CFU-Mix was decreased. Compared with the aged model, the number of cells entering G0/G1 phase and the percentage of SA-β-gal positive cells were decreased and the number of CFU-Mix was increased to Sca-1^＋ HSC/HPC in Rg1 aging treatment group and Rg1 aging prevention group. The expression of SIRT1 mRNA and protein was up-regulated and the expression of NF-κB mRNA and protein was down-regulated in Rg1 aging treatment group and Rg1 aging prevention group compared with the aged model. The changes of Rg1 aging prevention group was significantly higher than Rg1 aging treatment group. Conclusion： Rg1 could resist Sca-1^＋ HSC/HPC senescence during serial transplantation in which the signaling pathway of SIRT1-NF-κB may play an important role.