骨髓抑制是化疗的主要限制毒性，影响患者生存。造血干细胞衰老是骨髓抑制的主要机制, p16Ink4a-Rb信号通路是造血干细胞衰老的关键。课题组前期工作显示，龟鹿二仙胶可能通过抵抗骨髓造血干细胞的衰老来减轻化疗后的骨髓抑制，可以明显减少化疗后p16Ink4a的表达，但是单纯p53抑制剂干预并不能明显的逆转骨髓抑制。因此我们提出假说：龟鹿二仙胶通过抑制p16Ink4a-Rb通路来减轻化疗后骨髓造血干细胞衰老。我们将建立化疗后造血干细胞衰老动物模型，将龟鹿二仙胶作用于该模型大鼠进行体内研究，运用含药血清及过表达p16Ink4a基因进行体外细胞实验，从而明确龟鹿二仙胶减轻骨髓造血干细胞衰老的作用；进行p16 Ink4a-Rb信号通路上各蛋白及mRNA表达的检测，来深研究龟鹿二仙胶治疗化疗后骨髓造血干细胞衰老可能的分子机制，为中医药治疗化疗后骨髓抑制提供新的靶点。

Myelosuppression is the main limiting toxicity of chemotherapy and affects patient survival. Hematopoietic stem cell senescence is the main mechanism of myelosuppression, and the p16Ink4a-Rb signaling pathway is the key to hematopoietic stem cell senescence. Previous studies by our research group have shown, guilu erxian glue can reduce bone marrow suppression after chemotherapy by resisting the senescence of bone marrow hematopoietic stem cells,also can significantly reduce the expression of p16Ink4a after chemotherapy, but the intervention of p53 inhibitor can not significantly reverse the bone marrow suppression. So we make a hypotheses, guilu erxian glue can reduce chemotherapy induced bone marrow hematopoietic stem cell aging by inhibiting p16INK4a-Rb signaling pathway. We will establish a model of hematopoietic stem cell senescence after chemotherapy,.Guilu erxian glue will apply to the model rat in vivo,use drug-containing serum and over-express p16Ink4a gene in vitro，to clarify the role of guilu erxian glue in reducing chemotherapy induced bone marrow hematopoietic stem cell aging. Detect protein and mRNA expression in the p16 Ink4a-Rb signaling pathway,to deep study the molecular mechanism of guilu erxian glue in reducing chemotherapy induced bone marrow hematopoietic stem cell aging, which can provide a new target for the Chinese medicine treatment of bone marrow suppression after chemotherapy.