科研之友
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摘要
Objective: To evaluate the effect of Guilu Erxian Glue(龟鹿二仙胶,GEG) on cyclophosphamide(CTX)-induced bone marrow hematopoietic stem cells(HSCs) senescence in mice and explore the underlying mechanism. Methods: The H22 liver cancer ascites lump model was established in male Kunming mice by injecting intraperitoneally(i.p.) with 5×106/mL H22 cells per mouse. Fifty tumor-bearing mice were divided into the control, model, pifithrin-α, GEG, and GEG+pifithrin-α groups using a random number table, 10 mice in each group. CTX(100 mg/kg i.p.) was administrated to mice from day 1 to day 3(d1–d3) continuously except for the control group. The mice in the pifithrin-α, GEG and GEG+pifithrin-α groups were treated with pifithrin-α(2.2 mg/(kg·d) i.p.) for 6 consecutive days(d4–d9), GEG(9.5 g/(kg·d) i.p.) for 9 consecutive days(d1–d9), and GEG plus pifithrin-α, respectively. HSCs were collected after 9-d drug treatment. The anti-aging effect of GEG was studied by cell viability, cell cycle, and β-galactosidase(β-gal) assays. The mRNA and protein expressions of cyclin-dependent kinase 2(CDK2), CDK4, inhibitor of cyclin-dependent kinase 4 a encoding the tumor suppressor protein p16(p16INK4a), p21Cip1/Waf1, p53, and phosphorylated retinoblastoma(pRb) were evaluated by quantitative real-time reverse transcription-polymerase chain reaction and semi-quantitative Western blot, respectively. Results: Compared with the model group, GEG increased cell viability as well as proliferation(P<0.05 or P<0.01) and reduced β-gal expression. Furthermore, GEG significantly decreased the expressions of p16INK4a, p53 and p21Cip1/Waf1 proteins, and increased the expressions of CDK2, CDK4 and pRb proteins compared with the model group(P<0.05 or P<0.01). Conclusion: GEG can alleviate CTX-induced HSCs senescence in mice, and the p16INK4a-Rb signaling pathway might be the underlying mechanism.
