[1]蒋黎,兰林,李俊刚,等.HepaRG细胞移植治疗鼠特异性Fas抗体诱导的小鼠急性肝衰竭[J].陆军军医大学学报(原第三军医大学学报),2009,31(18):1724-1727.
 JIANG Li,LAN Lin,LI Jun-gang,et al.HepaRG cells engraftment treats acute liver failure in severe combined immuno-deficient mice after mouse-specific anti-Fas antibody inducement[J].J Amry Med Univ (J Third Mil Med Univ),2009,31(18):1724-1727.
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HepaRG细胞移植治疗鼠特异性Fas抗体诱导的小鼠急性肝衰竭(/HTML )
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陆军军医大学学报(原第三军医大学学报)[ISSN:1000-5404/CN:51-1095/R]

卷:
31卷
期数:
2009年第18期
页码:
1724-1727
栏目:
论著
出版日期:
2009-09-30

文章信息/Info

Title:
HepaRG cells engraftment treats acute liver failure in severe combined immuno-deficient mice after mouse-specific anti-Fas antibody inducement
作者:
蒋黎兰林李俊刚王宇明刘国栋
第三军医大学西南医院全军感染病研究所
Author(s):
JIANG Li LAN Lin LI Jun-gang WANG Yu-ming LIU Guo-dong
Institution of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038, China
关键词:
肝细胞移植Fas抗体/Jo2 mAb急性肝衰竭动物模型/鼠
Keywords:
hepatocytes transplantation anti-Fas antibody/Jo2 mAb acute liver failure animal model/mouse
分类号:
R-332;R575.3;R617
文献标志码:
A
摘要:
目的   探讨HepaRG细胞移植对鼠特异性Fas抗体诱导的急性肝衰竭小鼠的治疗作用和人肝细胞异种移植的策略。   方法   利用特异性鼠抗Fas抗体(Jo2 mAb)腹腔注射,剂量为0.3 mg/kg,诱导20只SCID小鼠制备急性肝衰竭模型,24 h内按照实验动物随机数字表分组方法,经脾移植2×106 HepaRG细胞的小鼠为实验组(10只),未经HepaRG细胞移植的小鼠为对照组(10只)。观察小鼠的存活率、肝脏功能、肝组织变化情况。实验组移植4周免疫组化检测肝组织人白蛋白、人CK18、人Hep Par 1的表达,免疫荧光检测人白蛋白的表达。   结果   实验组小鼠有9只存活超过4周,而对照组小鼠3 d内先后死亡9只,实验组血清ALT和AST趋于正常,显著低于对照组(P<0.01),且存活时间显著高于对照组(P<0.01)。实验组经HepaRG细胞移植能避免Jo2 mAb所致肝组织出血、坏死,移植后4周免疫组化可见人白蛋白、CK18、Hep Par 1阳性表达细胞,肝组织免疫荧光可见人白蛋白阳性细胞的表达。   结论   移植HepaRG细胞可治疗Jo2 mAb腹腔注射小鼠诱导的急性肝衰竭,HepaRG细胞不仅在小鼠肝内存活,且得以增殖。
Abstract:
Objective   To investigate the effect of engrafting human liver cancer cell line HepaRG on mouse-specific anti-Fas monoclonal antibody (Jo2 mAb) induced acute liver failure(ALF) in the severe combined immunodeficient (SCID) mice and investigate the heteroplastic strategy of human hepatocyte.    Methods   ALF was induced by injecting Jo2 mAb (0.3 mg/kg) intraperitoneally in SCID mice. Mice from experimental group (n=10)received 2×106 HepaRG cells engraftment in the spleen within 24 h after Jo2 mAb administration, and another 10 ALF mice served as control. The survival rate of mice, liver function and liver morphology of all mice were observed. At 4 weeks post-engraftment, HepaRG cells was characterized by S-P immunohistochemical staining for human albumin, human cytokeratin 18 and human Hep Par 1, meanwhile, immunofluorescence staining for human albumin.    Results   Nine transplanted mice were survival in 4 weeks after treatment and 9 non-transplanted mice were dead successively within 3 d. Compared to control group, survival time was prolonged significantly and serum liver enzyme levels was reduced significantly either of experimental group (P<0.01). HepaRG cells engraftment protected mice from Jo2 mAb mediated liver hemorrhage and hepatocyte apoptosis in contrast to matched nonengrafted mice. In 4 weeks post-engraftment, human albumin, CK18 and specific human Hep Par 1 were found by immunohistochemistry staining, so was human albumin by immunofluorescence staining.    Conclusion    HepaRG cells transplantation prolongs the survival time and attenuates histological changes of Jo2 mAb-induced ALF mice. The transplanted HepaRG cells may well survive and regenerate for some period.

相似文献/References:

[1]王志毅,张艳,石小枫,等.肝细胞移植联合肝再生增强因子治疗大鼠急性肝功能衰竭的研究[J].陆军军医大学学报(原第三军医大学学报),2007,29(10):899.
 WANG Zhi-yi,ZHANG Yan,SHI Xiao-feng,et al.Combining hepatocyte transplantation intraperitoneally and augmenter of liver regeneration for acute hepatic failure in rats[J].J Amry Med Univ (J Third Mil Med Univ),2007,29(18):899.
[2]蒋黎,毛青,王宇明,等.建立人鼠嵌合肝动物模型的实验研究[J].陆军军医大学学报(原第三军医大学学报),2005,27(09):856.

更新日期/Last Update: 2009-09-16