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小牛脾提取物改善环磷酰胺诱导的小鼠白细胞减少症和抑制HL60细胞的糖酵解作用

胡振宇, 刘晓岩, 刘秀梅, 杨振军*, 王银叶*   

  1. 1. 北京大学医学部 药学院 分子与细胞药理学系, 100191 北京
    2. 北京大学医学部 天然药物及仿生药物国家重点实验室; 药学院 药物化学系, 北京 100191

  • 收稿日期:2010-12-02 修回日期:2011-02-15 出版日期:2011-03-15 发布日期:2011-03-15
  • 通讯作者: 杨振军*, 王银叶*

Calf spleen extract alleviates cyclophosphamide-induced leucopenia in mice and inhibits the glycolysis of HL60 cells

Zhen-Yu Hu, Xiao-Yan Liu, Xiu-Mei Liu, Zhen-Jun Yang*, Yin-Ye Wang*   

  1. 1. Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
    2. State Key Laboratory of Natural and Biomimetic Drugs; Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
  • Received:2010-12-02 Revised:2011-02-15 Online:2011-03-15 Published:2011-03-15
  • Contact: Zhen-Jun Yang*, Yin-Ye Wang*

摘要:

小牛脾提取物为临床治疗肿瘤的辅助药物, 可以改善患者的生理状态, 但是其作用机制尚不明确。我们评价了小牛脾提取物对小鼠白细胞减少症和HL60细胞生长的影响。10 mL/kg (2.5 mg生物活性多肽和190 μg核糖/mL) 小牛脾提取物可显著增加白细胞减少症小鼠的白细胞数量, 尤其是中性粒细胞的数量; 小牛脾提取物在体外明显刺激骨髓细胞增殖和下调血清中的GM-CSF水平。此外, 小牛脾提取物可以明显抑制HL60细胞增殖并降低乳酸和ATP的生成; 同时可以明显诱导HL60细胞凋亡和细胞周期S期阻滞。研究结果提示: 小牛脾提取物可以明显升高白细胞数量, 其机制可能与直接刺激骨髓细胞增殖相关; 小牛脾提取物可以抑制HL60细胞生长, 其作用机制可能与诱导细胞凋亡, 细胞周期阻滞和抑制细胞糖酵解作用有关。该研究结果揭示了小牛提取物新的作用和机制, 对于扩展小牛脾提取物的临床应用有重要价值

关键词: 白细胞减少症, 糖酵解, 细胞凋亡, 细胞周期阻滞, 小牛脾提取物

Abstract: Calf spleen extract (CSE) has been clinically used as an adjuvant agent in malignant tumor therapy. It can improve the physical status of patients. However, its mechanism of action remains relatively unclear. In this study, we investigated the effect of CSE on leucopenia in mice and on promyelocytic leukemia cells (HL60). CSE in 10 mL/kg (2.5 mg bioactive polypeptides and 190 μg ribose/mL) significantly increased leukocyte numbers in leucopenia mice. The effect on neutrophil numbers, among all leukocytes, was the most evident. CSE stimulated the proliferation of bone marrow cells in vitro and decreased the GM-CSF level in serum. In addition, CSE significantly reduced the viability of HL60 cells, decreased the production of lactate and adenosine triphosphate (ATP) of these cells. CSE induced the apoptosis and S-phase arrest in HL60 cells. In conclusion, CSE can enhance leukocyte numbers, which may be attributed to its direct stimulatory effect on bone marrow cells. CSE is an inhibitor of promyelocytic leukemia cell viability, which may be attributed to the induction of the apoptosis, the arrest of cell cycle and the inhibition of the glycolysis of cells.

Key words: Leucopenia, Glycolysis, Apoptosis, Cell cycle arrest, Calf spleen extract

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*Corresponding author. Tel.: 86-10-82802652; fax: 010-62015584