HSP60及TLR4信号途径在小鼠心脏移植物中的表达及意义  

Expression and significance of HSP60 and Toll-like receptor 4 signal transduction in mouse heart transplantation

作　　者：陈家军[1] 吴宏妍[1] 孙宗全[2] 聂荣华[1] 吴富常[1] 张增旺[1] 

机构地区：[1]襄樊市中心医院心胸外科,湖北襄樊441021 [2]华中科技大学同济医学院附属协和医院心外科,湖北武汉430022

出　　处：《中国病理生理杂志》2010年第4期625-629,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30471715)

摘　　要：目的:检测HSP60及TLR4信号途径在小鼠心脏移植物中的表达情况,探讨其在心脏移植排斥反应中的作用以及它们之间的关系。方法:建立小鼠颈部心脏移植模型,随机分为2组:对照组(同系移植组),供、受体均为C57BL/6小鼠;实验组(同种异品系移植组),供、受体分别为BALB/c、C57BL/6小鼠。分别于移植后第3d、第7d取小鼠心脏及血液标本,免疫组化及Western blotting检测心脏移植物HSP60、TLR4、MyD88及NF-κB的表达情况,ELISA法检测小鼠血液肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)和白细胞介素-12(IL-12)的浓度,病检分析心脏组织形态学改变。结果:实验组心脏移植物HSP60、TLR4、MyD88、NF-κB的表达及TNF-α、IFN-γ、IL-12的浓度明显高于对照组;病理学检查结果显示实验组小鼠在术后第3、7d分别发生轻、重度排斥,对照组无明显排斥现象。结论:心脏移植后HSP60表达增强,可能通过TLR4以MyD88依赖的方式激活TLR4信号途径,从而促进移植排斥反应的发生,调控HSP60及其受体后信号途径可能为抗排斥反应提供新思路。AIM：To investigate the expression of heat shock protein 60（HSP60） and Toll-like receptor 4 transduction system in mouse cardiac transplantation. METHODS： The mouse cervical heart transplantation model was established. The animals were divided into control group （the donor and recipient were all C57BL/6 mice） and experimental group （the donor was BALB/c mice and recipient was C57BL/6 mice）. The heart and blood were collected for study at 3 d and 7 d. The pathological analysis of the hearts was performed. The levels of cytokines in the serum were determined using ELISA. The expression of HSP60,TLR4,MyD88 and NF-κB in the myocardium was determined by immunohistochemistry and Western blotting. RESULTS： The expression levels of HSP60,TLR4,MyD88 and NF-κB were higher in experimental group than those in control group. Severe rejection was observed in experimental group,whereas no distinct rejection in control group was found. The cytokines （TNF-α,IFN-γ,IL-12） increased significantly in experimental group as compared to those in control group. CONCLUSION： HSP60 increases significantly after heart transplantation,which may activate Toll-like receptor 4 transduction system in a MyD88-dependent pathway and promote allograft rejection. Regulation of HSP60 signal transduction may be a novel way for treating allograft rejection.

关 键 词：热休克蛋白60 受体 Toll-样 心脏移植 细胞因子类 NF-κB 

分 类 号：R392.4[医药卫生—免疫学]