粒细胞集落刺激因子治疗失代偿期肝硬化的机制及疗效研究

目的 探讨应用粒细胞集落刺激因子(G-CSF)动员治疗失代偿期肝硬化的疗效及其机制.方法 采用流式细胞术和酶联免疫吸附法,对不同类型慢性HBV感染者外周血中造血干细胞及其受体的表达和干细胞迁移相关细胞因子的水平进行检测;对应用G-CSF动员治疗前后患者造血干细胞受体的表达以及肝功能变化进行动态观察.结果 与正常对照组比较,乙型肝炎肝硬化患者的CD34+细胞比例明显升高,差异有统计学意义(0.21±0.09)% vs.(0.30±0.13)%;F=5.45,P=0.006];慢性乙型肝炎患者和乙型肝炎肝硬化患者基质细胞衍生因子1α(SDF-1α)、干细胞因子(SCF)、基质金属蛋白质酶-9(MMP-9)的表达水平明显升高(F＝13.65,P=0.001;F=23.28,P=0.000;F=18.98,P=0.000).与治疗前比较,G-CSF动员治疗后患者的CD34+干细胞比例明显增加(0.31±0.14)% vs.(0.95±0.46)%,(0.81±0.37)%;F=20.33,P=0.000];治疗后患者外周血中SCF及MMP-9的表达水平明显升高(F=4.52,P=0.015;F=3.85,P=0.027).治疗组与对照组比较,治疗前后TBil、ALB以及PT的变化水平差异均无统计学意义,两组患者的治愈好转率也无明显差异.结论 乙型肝炎肝硬化患者存在基础水平的造血干细胞动员,可能与肝脏损伤的修复有关;G-CSF可通过调控干细胞动员相关因子的表达水平,促进肝硬化患者的造血干细胞动员;G-CSF动员治疗对改善乙型肝炎肝硬化患者的生化指标及短期预后无明显效果.

Mechanism and efficacy of mobilization of granniocyte colony-stimulating factor in the treatment ofdecompensated liver cirrhosis

Objective To explore the efficacy of granulocyte colony-stimulating factor（G-CSF） mobilization in the treatment of decompensated liver cirrhosis and the mechanism of its action. Methods The proportions of cluster-of-differentiation（CD）-34 ＋ cells and their receptor-CXCR4 ,were detected by flow cytometry in patients with different types of chronic HBV infection. The levels of chemokines and cytokines were measured by enzyme-Iinked immunosorbent assay. Results The proportion of CD34＋ cells in patients with cirrhosis was significantly increased compared with the healthy controls （0. 30 ± 0. 13 ） % vs. （ 0. 21± 0. 09 ） %, P 〈 0.05 ]. The expression levels of SDF-lα,SCF,and MMP-9 were significantly elevated in patients with chronic hepatitis B and liver cirrhosis （P 〈 0. 01 ）. The proportion of CD34＋ cells in patients with cirrhosis was increased obviously after treatment by G-CSF mobilization（ P 〈 0. 01 ）. The expression levels of SCF and MMP-9 were significantly elevated in the peripheral blood of patients with liver cirrhosis after treatment with G-CSF （P 〈 0. 05 ）. No significant differences were found in the levels of total bilirubin, albumin, and prothrombin time between the treated and control groups; Furthermore, no significant differences were observed in the cure and improvement rates between the two groups. Conclusions （1） The basal levels of stem cell mobilization in patients with liver cirrhosis might be associated with the repair of liver injury. （2）G-CSF could promote hematopoietic stem cell mobilization through the regulation of the expression level of stem-cell-mobilization-related factors in patients with liver decompensated cirrhosis. （3）No apparent effects of G-CSF therapy on both liver function and short-term prognosis in patients with liver cirrhosis were confirmed.