Th1/Th17失衡在小鼠急性移植物抗宿主病中的作用研究  

Significance of Th1 /Th17 Imbalance in Mice with Acute Graftversus-Host Disease

作　　者：姚瑶[1] 潘彬[1] 边月平 夏丹丹[1] 程海[1] 宋国梁[1] 曾令宇[1] 徐开林[1] 

机构地区：[1]徐州医学院附属医院血液科,江苏徐州221002

出　　处：《中国实验血液学杂志》2015年第5期1488-1492,共5页Journal of Experimental Hematology

基　　金：国家自然科学基金(81302034;81300377)

摘　　要：目的:观察Th1和Th17细胞亚群失衡对小鼠急性移植物抗宿主病(graft-versus-host disease,GVHD)发病的影响。方法:在小鼠异基因骨髓移植模型中,应用小剂量常山生物碱衍生物(halofuginone,HF)进行干预以改变Th1/Th17平衡。分别设立无药物干预的对照组(GVHD组)和联合应用HF干预组(GVHD+HF组)。移植后连续观察受鼠的生存率和急性GVHD临床评分,监测外周血中Th1、Th17细胞含量,Th1/Th17比率,以及IFN-γ和IL-17A的浓度。分析肝脏和小肠组织中IFN-γ和IL-17A的相对表达水平,以及相应的GVHD病理学改变。结果:应用小剂量HF可增加受鼠外周血中的Th1/Th17比率、死亡率和临床表现评分(P<0.05);急性GVHD临床评分与外周血中的Th1/Th17比率呈正相关关系(P<0.001);应用小剂量HF可降低小肠内IL-17A的表达水平并增加小肠内IFN-γ的表达水平(P<0.05),加重小肠的GVHD损伤,同时,HF亦可增加肝脏IFN-γ的表达水平(P<0.05)并加重肝脏GVHD损伤。结论:Th1/Th17亚群失衡与小鼠急性GVHD的发生密切相关。Objective : To investigate the effects of Th1 /Th17 cell imbalance on the pathogenesis of acute graftversushost disease( GVHD) in mice. Methods: In a murine GVHD model of C57 BL /6( H- 2b),a low dose of halofuginone( HF) was applied for treating the recipients in order to result in Th1 /Th17 imbalance. Rechipient mice were divided into GVHD group( without HF intervention) and GVHD plus HF group( treated by HF). The recipients were monitored for survival rate,clinical scores of acute GVHD,contents of circulatory Th1 and Th17 cells,Th1 /Th17 ratio and serum level of IFN-γ and IL-17 A. Expression levels of IFN-γ and IL-17 A in target organs were analyzed by using real-time PCR,and the target organs were delivered for histological examinations. Results: Recipients treated with HF showed that all the mortality,circulatory Th1 /Th17 ratio and clinical score were higher than those in the mice without HF intervention( P < 0. 05). Circulatory Th1 /Th17 ratio positively correlates with clinical score( P < 0. 001).HF administration reduces the expression level of intestinal IL-17 A and increases intrahepatic and intestinal IFN-γ level( P < 0. 05),HF treatment aggravates GVHD in liver and small intestine with augmented hepatic and intestinal inflammation. Conclusion: Th1 /Th17 imbalance contributes to the pathogenesis of acute GVHD.

关 键 词：移植物抗宿主病 TH1细胞 TH17细胞 Th1/Th17比率 

分 类 号：R457.7[医药卫生—治疗学]