目的 探讨人参皂苷Rg₁在造血干/祖细胞（HSC/HPC）连续移植中抗细胞衰老的作用机制。方法 免疫磁性分选法分离纯化的雄性供体小鼠Sca-1⁺HSC/HPC连续移植3代构建HSC/HPC衰老体内模型。经⁶⁰Co γ射线致死剂量辐射的雌性受体小鼠分成4组：对照组、模型组、人参皂苷Rg₁（20 mg/kg）治疗给药组、人参皂苷Rg₁（20 mg/kg）预防给药组，每天给药1次，连续给药30 d。荧光定量PCR法检测各组小鼠Sca-1⁺HSC/HPC p16^INK4a、p19^Arf、p53、p21^Cip1/Waf1基因的表达，Western blotting法检测p16^INK4a、p21^Cip1/Waf1、CDK4、CDK2、CyclinD1、Cyclin E蛋白的表达。结果 与模型组比较，各代移植Sca-1⁺HSC/HPC雌性小鼠中，人参皂苷Rg₁治疗给药组及预防给药组小鼠Sca-1⁺HSC/HPC p16^INK4a、p19^Arf、p53、p21^Cip1/Waf1基因及p16^INK4a、p21^Cip1/Waf1、CyclinD1蛋白表达下调；CDK4、CDK2、CyclinE蛋白表达上调。人参皂苷Rg₁预防给药组小鼠各项检测指标的改善均优于其治疗给药组。结论 人参皂苷Rg₁可能通过调控p16^INK4a-Rb和p19^Arf-p53-p21^Cip1/Waf1信号转导通路，对Sca-1⁺HSC/HPC连续移植衰老模型发挥拮抗作用。

Objective To investigate the mechanism of ginsenoside Rg₁ against the hematopoietic stem/progenitor cell (HSC/HPC) senescence during serial transplantation. Methods Male mice Sca-1⁺HSC/HPC isolated and purified by magnetic activated cell sorting (MACS) were transplanted for three generations to establish aging in vivo model of mice. The female recipient mice radiated lethal dose from ⁶⁰Co γ ray were divided into four groups: the control, model, Rg₁-treated (20 mg/kg), and Rg₁ prevention (20 mg/kg) groups. The mice were administered once daily for 30 d. The expression of p16^INK4a, p19^Arf, p53, and p21^Cip1/Waf1 mRNA was detected by quantitative PCR. The expression of p16^INK4a, p21^Cip1/Waf1, CDK4, CDK2, CyclinD1, and CyclinE proteins was examined by Western blotting. Results Compared with the model group, the expression of p16^INK4a, p19^Arf, p53, p21^Cip1/Waf1mRNA and p16^INK4a, p21^Cip1/Waf1, CyclinD1 proteins was down-regulated, and the expression of CDK4, CDK2, and CyclinE proteins was up-regulated in both Rg₁-treated and Rg₁ prevention groups. The all index changes of mice in Rg₁ prevention group were significantly higher than those of mice in Rg₁-treated group. Conclusion Rg₁ could prevent and treat the Sca-1⁺HSC/HPC senescence during serial transplantation in which the signaling pathways of p16^INK4a-Rb and p19^Arf-p53-p21^Cip/Waf1 may play an important role.

国家自然科学基金资助项目（30973818，81202785）