外周血造血干细胞移植与粒细胞集落刺激因子动员治疗急性肝衰竭的疗效比较

Comparative research on peripheral blood hematopoietic stem cell transplantation and granulocyte colony stimulating factor mobilization in acute hepatic failure

目的观察外周血造血干细胞移植(PBHSCT)及重组人粒细胞集落刺激因子(rhG-CSF)动员后对大鼠急性肝衰竭的疗效,并探讨其机制。方法采用D-氨基半乳糖(D-Gal)诱导大鼠急性肝衰竭模型,随机分为3组。对照组(Ⅰ组):尾静脉及肌肉均注射0.9%氯化钠注射液;rhG-CSF单纯动员组(Ⅱ组):造模前24h、12h、4h及造模同时皮下注射rhG-CSF,尾静脉及肌肉均注射0.9%氯化钠注射液;异体外周血造血干细胞移植组(Ⅲ组):正常大鼠连续5 d皮下注射rhG-CSF,第6天分离外周血造血干细胞,造模后24 h尾静脉注射外周血造血干细胞,肌肉注射环孢霉素A(CsA)。观察各组存活率、肝功能、肝脏病理变化。结果Ⅱ组和Ⅲ组存活率显著高于Ⅰ组(<0.01),但Ⅱ组和Ⅲ组间差异无统计学意义(>0.05)。肝功能及病理情况在Ⅱ组和Ⅲ组均有明显改善,但两者间差异无统计学意义。结论应用外周血造血干细胞移植及G-CSF均能有效治疗大鼠急性肝衰竭,改善D-Gal诱导的肝衰竭大鼠的存活率,促进肝功能恢复及改善肝脏病理状况。

Objective To investigate the effects of peripheral blood hematopoietic stem cell transplantation（PBHSCT） and recombinant human granulocyte colony stimulating factor（rhG-CSF） after mobilization on acute hepatic failure of rats,and to explore their mechanism.Methods Acute hepatic failure rats induced by D-gal,were randomly divided into three groups ： control group（group Ⅰ： rats was received intravenously normal saline and intramuscularly normal saline daily）,rhG-CSF simple mobilization group（groupⅡ ： rats were injected subcutaneously with rhG-CSF at 24 h,12 h,4 h,0 h before the D-gal injection,intravenously with nomal saline and intramuscularly with physiological saline daily 24 h after the D-gal injection）,and PBHSCT group（group Ⅲ： normal rats were injected subcutaneously with rhG-CSF daily,for five days,and on the sixth day were taken blood which was obtained PBHSC,then were given intravenously with PBHSC 24h after the D-gal injection,while intramuscularly with CsA daily）.Survival rate,hepatic function,and liver pathological changes were observed.Results The survival rate in group Ⅱ and group Ⅲ was significantly higher than that of group Ⅰ（ 0.01）,but there was no significant difference between group Ⅱ and group Ⅲ（ 0.05）.Hepatic function and pathological state of rats were improved significantly in group Ⅱ and group Ⅲ.Conclusions PBHSCT and granulocyte colony stimulating factor both can effectively treat rats with acute hepatic failure,improve the survival rate,ameliorate hepatic function and liver pathological state