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

[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。

[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% CCIA 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 CD34 contained 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.