重组人粒细胞集落刺激因子对肝硬化大鼠外周血干细胞动员的研究

Preliminary study on mobilization of hepatic stem cells of CCL4-induced liver cirrhosis rats by recombinant human granulocyte-Colony stimulating factor

关键词:  粒细胞集落刺激因子（G-CSF）  干细胞  CD34细胞动员

Key words:  granulocyte colony stimulating factor  hepatic stem cells  CD₃₄^＋ cell mobilization

摘要:

［目的］ 观察重组人粒细胞集落刺激因子(rhG-CSF)对四氯化碳(CCL₄)肝硬化大鼠外周血中CD34⁺细胞的动员作用，以及对肝硬化大鼠肝脏生化学的影响，寻求一种安全有效、不加重肝损伤的动员CD₃₄⁺细胞的方法。［方法］ 50% CCL₄橄榄油溶液建立肝硬化大鼠模型，rhG-CSF动员组大鼠皮下注射rhG-CSF10μg·kg^-1·d^－1，共计5d，对照组给予相同剂量生理盐水。流式细胞仪测定外周血单个核细胞中的CD₃₄⁺细胞的比例，同时检测ALT、AST、T-BIL和ALB,观察G-CSF对肝硬化大鼠肝脏的影响。 ［结果］ 肝硬化大鼠rhG-CSF动员后外周血CD₃₄⁺细胞占单个核细胞（CD34+/MNC）比例（4.08±1.38）％是生理盐水对照组(0.43±0.21）%的9.5倍；而生化学检测两组没有显著性差异。［结论］G-CSF动员能促进更多的骨髓/造血干细胞源性的肝干细胞在外周血中表达，而且不加重肝硬化大鼠的肝脏损伤。

Abstract:

［Objective］ To study the changes of CD₃₄^＋ cells in the liver and peripheral blood, and the biochemistric changes of the livers of CCL4-induced cirrhosis rats mobilized by recombinant human granulocyte-colony stimulating factor (rhG-CSF). To explore a safe and effective method of mobilization of hepatic stem cells without worsening liver damage.［Methods］ First established the cirrhosis rat model with 50% CCL4 solution, and confirmed it by histopathology. Then rhG-CSF was administrated subcutaneously at dose of 10 μg/kg.L for 5 days, whereas the control cirrhosis rats recept injection with natrium saline. On day 6, we examined the quantity of CD₃₄⁺ cells contained in mononuclear cells (MNC) by flow cytometry. At the same time, we examined liver function including ALT,AST,TBIL and ALB by serum biochemistry.［Results］ After mobilization of rhG-CSF of CCL4-induced liver cirrhosis rats，the quantity of CD₃₄contained in mononuclear cells increased apparently, which was 9.5 folds than that of the control rats administered with natrium saline(4.08±1.38)% vs(0.43±0.21)%. The liver function of two group was the same without statistical significance. ［Conclusions］ RhG-CSF mobilization can't increase can mobilize more bone marrow/hematopoietic progenitor cells-derived hepatic stem cells to peripheral blood and do not worsen the liver damage of cirrhosis rats.