文章摘要
吴 迪,张 伟,刘亚林,习杰英.TLR4与小鼠半相合造血干细胞移植后急性GVHD关系的实验研究[J].南京医科大学学报,2013,(4):462~466
TLR4与小鼠半相合造血干细胞移植后急性GVHD关系的实验研究
The relationship between TLR4 and acute graft-versus-host disease in murine haploidentical hematopoietic stem cell transplantation model
投稿时间:2012-11-14  
DOI:10.7655/NYDXBNS20130408
中文关键词: Toll样受体  造血干细胞移植  急性移植物抗宿主病
英文关键词: TLR4  transplantation of hematopoietic stem cell  acute GVHD
基金项目:
作者单位
吴 迪 西安交通大学医学院第一附属医院血液科,陕西 西安 710061 
张 伟 西安市第四医院外科,陕西 西安 710004 
刘亚林 西安交通大学医学院第一附属医院血液科,陕西 西安 710061 
习杰英 西安交通大学医学院第一附属医院血液科,陕西 西安 710061 
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中文摘要:
      目的:探讨Toll样受体4(Toll-like receptor 4,TLR4)对半相合造血干细胞移植(HSCT)小鼠急性移植物抗宿主病(acute graft-versus-host disease,a-GVHD)的影响及其可能机制。方法:建立小鼠半相合HSCT模型,随机分为分为实验1组(n=12):每只小鼠按20 μg/kg输注TLR4激动剂-脂多糖(LPS);实验2组(n=12):每只小鼠按20 μg/kg 输注TLR4单克隆抗体;对照组(n=12):其中6只小鼠按20 μg/kg 输注灭菌生理盐水,另6只半相合HSCT 移植后不作任何处理。观察各组小鼠的a-GVHD临床表现及生存时间,检测小鼠血清中白细胞介素-1β(IL-1β)?肿瘤坏死因子-α(TNF-α)变化情况,并于移植后14 d对小鼠肝脏进行病理分析。结果:与对照组相比较,实验2组的GVHD严重程度?生存率以及病理改变均明显轻于对照组(P < 0.05),而实验1组的上述改变则明显较对照组为重。结论:针对TLR4的抑制剂对半相合HSCT小鼠的a-GVHD具有一定的预防作用。
英文摘要:
      Objective:To investigate the effect of Toll-Like receptor 4(TLR4) on the severity of acute graft-versus-host disease(GVHD) after haploidentical stem cell transplantation (HSCT) in mouse and explore its potential mechanism. Methods:Establish a mouse model of MHC haploidentical bone marrow transplantation. The mice were randomly divided into the experimental group 1(n=12):each mouse was received 20 μg/kg infusion of TLR4 agonist LPS; the experimental group 2(n=12):each mouse was received 20μg/kg infusion of TLR4 monoclonal antibody; the control group(n=12):six mice were received 20 μg/kg infusion of sterile saline; other six mice without any treatment after transplantation. We observed the clinical manifestation of GVHD and the survival rate by using Kaplan-Meier analysis. On the 14th day after transplantation,the histopathology of GVHD was evaluated in the liver,and the change of serum IL-1β,TNF-α was detected. Results:Compared with the control group,the mice in the experimental group 2 had reduced severity of acute GVHD symptoms,improved survival rate(P < 0.05) and less histopathological evidence of GVHD. Correspondingly,the above changes of the mice in the experimental group 1 were severe. Conclusion:The TLR4 inhibitors can prevent acute GVHD in murine haplo-HSCT model.
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