中文摘要：

目的 探讨人参皂苷Rg1在造血干/祖细胞（HSC/HPC）连续移植中对抗细胞衰老的作用与去乙酰化酶6/核因子-κB（SIRT6/NF-κB）信号轴的关系。方法 免疫磁性分选法分离纯化雄性供体小鼠干细胞抗原阳性（Sca-1＋）HSC/HPC,连续移植3代构建HSC/HPC衰老体内模型。60Coγ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;Rg1预防衰老组。造血祖细胞混合集落（CFU-Mix）培养,细胞周期分析和衰老相关β-半乳糖苷酶（SA-β-Gal）染色分析Rg1体内调控Sca-1＋HSC/HPC衰老的作用。实时定量PCR及Western blotting检测衰老调控分子SIRT6、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SIRT6/NF-κB信号轴发挥其对抗连续移植过程中Sca-1＋HSC/HPC衰老的作用。

英文摘要：

Objective To investigate the effect of sirtuin （SIRT）6/nuclear factor（NF）-KB signaling pathway in delaying hematopoietic stem cell （HSC） and progenitor cell （HPC） senescence with ginsenoside Rgl during serial transplantation. Methods Sca-1 ＋HSC/HPC from male donator mouse was isolated and purified by magnetic activated cell sorting （MACS）. Sea-1 ＋ HSC/HPC replicability aged model in vivo was established through the Sca-1 ＋ HSC/HPC serial transplantation. The femal recipient mice radiated lethal dose from 60Coγ ray were divided into four groups： the control group, the aged model group, the Rgl treat aged group and the Rgl prevent aged group. The effect of Rgl to delay Sca-1 HSC/HPC senencence in vivo was evaluated by senescence-associated β-galactosidase （SA-β-gal） staining, mixed hematopoietic progenitor cell culture and cell cycle assay. The expressions of SIRT6 and NF-KB mRNA and protein were detected by quantitative PCR and Western blotting. Results With the increasing of transplantation, Sca-1 ＋ HSC/HPC appeared aging characters. The number of ceils entered G0/Gl phase and the percentage of SA-β-gal positive cells wasincreased, and the number of CFU-Mix was decreased. Compared with the aged model group, the number of cells entered 60Coγ phase and the percentage of SA-β-gal positive cells were decreased, the number of CFU-Mix was increased to Sca-1 ＋HSC/HPC in Rgl treat aged group and Rgl prevent aged group, the expression of SIRT6 mRNA and protein was up regulated and the expression of NF-KB mRNA and protein was down regulated in Rgl treat aged group and Rgl prevent aged group. The changes of Rgl prevent aged group was significantly higher than Rgl treat aged group. Conclusion Rgl could resist Sca-1 ＋ HSC/HPC senescence during serial transplantation in which the signaling pathway of SIRT6-NF-KB may play an important role.