摘要
目的:观察重组人粒细胞集落刺激因子(rhG- CSF)对CCl_4所致小鼠肝损伤的保护和治疗作用以及探讨rhG-CSF动员的外周血干细胞在受损肝组织内定植的能力方法:清洁级BALB/c小鼠,ip 400mL/LCCl_4,2mL/kg,每周2次,诱导肝损伤,sc rhG-CSF 200μg/kg进行预防和治疗.观察各实验组小鼠的生存率、肝组织病理变化、肝功能等指标.分别用免疫组化及流式细胞术观察肝组织中Thy-1和CD34阳性细胞变化,用Y染色体原位杂交法观察rhG-CSF动员的♂小鼠外周血干细胞在肝受损伤的♀小鼠肝脏内的定居能力.结果:rhG-CSF预防组小鼠的生存率、肝组织病理改变、肝功能的酶学指标均好于模型组(P<0.05).治疗后30d,rhG-CSF治疗组小鼠血清中肝功能酶学指标ALT和AST与对照组相比分别有显著性意义(1033.5±350.1nkat/L vs 1983.7±616.8nkat/L,P<0.01;1817.0±483.4 nkat/L vs 3017.3±811.2nkat/L,P<0.05),治疗后8d、15d rhG-CSF组肝脏组织中Thy-1^+和CD34^+细胞明显多于对照组(P<0.05).接受♂小鼠外周血干细胞移植的♀小鼠肝组织可见Y染色体阳性的细胞,主要位于汇管区与中央静脉周围,少数位于脾脏.结论:rhG-CSF预防和治疗均能促进CCl_4所致的小鼠肝损伤修复,提高生存率.
AIM： To observe the effect of recombinant human granulocyte colony stimulating factor （rhG-CSF） on repair of CCl4-induced liver injury in mice, and to investigate the homing ability of peripheral blood stem cells mobilized by rhG- CSF to localize in the injured liver.
METHODS： Liver injury was induced by 400 mL/L CCl4 2 mL/kg in clean BALB/c mice twice a week and then treated. Then, with rhG- CSF 200 μg/kg sc. The mortality rate and liver pathology changes and liver functions and other factors were analyzed. Detection of CD34^± and Thy-1^± cells were performed with flow-cytometry and immunohistochemical staining respectively, The situ hybridization for Y chromosome in liver was tested to determine the homing ability of the peripheral blood stem cells of male mice mobilized by rhG-CSF to the injured liver of female mice.
RESULTS： Compared with the liver injury group, the mortality rate and changes in liver histology and function in the rhG-CSF preven- tion group were significantly lower （P 〈 0.05）. Alanine aminotransferase and aspartate aminotransferase were significantly lower in the rhG-CSF treatment group at 30 days after CCl4 discontinuation than in the control group （1033.5 ± 350.1 nkat/L vs 1983.7 ± 616.8 nkat/L, P 〈 0.01; 1817.0 ± 483.4 nkat/L vs 3017.3 ±811.2 nkat/L, P 〈 0.05）. Compared with the control group, Thy-1^＋ and CD34^＋ cells in the liver of the rhG- CSF treatment group were increased on days 8 and 15 （P 〈 0.05）. In situ hybridization in the liver of female mice transplanted with peripheral stem cells from male mice revealed that Y-chromosome- positive cells were found in the injured liver, which were mainly seen around the duct area and central vein, and a few in the spleen.
CONCLUSION： rhG-CSF prevention and treatment significantly promote recovery and improve survival after CCl4-induced liver injury.
出处
《世界华人消化杂志》
CAS
北大核心
2007年第32期3395-3402,共8页
World Chinese Journal of Digestology
基金
河北省科技攻关题资助项目
No.052761262
关键词
粒细胞集落刺激因子
骨髓干细胞
肝损伤修复
Y染色体
Granulocyte colony stimulating factor
Bone marrow stem cell
Liver injury
Liver repair
Y chromosome
