摘要
目的:探讨心脏移植慢性排斥反应的发病机制。方法:通过DSBT(DonorSpecificBloodTransfusion)诱导耐受,建立同种异体大鼠心脏移植慢性排斥的模型。采用免疫组化和Northernblot方法检测大鼠心脏移植慢性排斥反应时浸润细胞的表型及分布,胞间黏附分子和生长因子的表达。结果:慢性排斥组的心肌CD45+、CD4+、CD8+、TCR+、CD45RB+细胞、巨噬细胞和NK细胞显著升高。这些细胞主要分布在心肌间质、血管周围和心内膜下区域,并以T淋巴细胞和巨噬细胞为主。在损伤区域可见Ⅰ型细胞间黏附分子(ICAM1)、Ⅰ型淋巴细胞功能性抗原(LFA1)、碱性成纤维细胞生长因子(bFGF)和转化生长因子β1(TGFβ1)表达增强。TGFβ1mRNANorthernblot分析,慢性排斥组比正常对照组升高5～6倍。结论:T细胞和巨噬细胞在心脏移植慢性排斥的损伤中起主要作用,ICAM1、LFA1、bFGF和TGFβ1也参与了心脏移植物血管病(Cardiacallograftvasculopaphy,CAV)的形成。
Objective:To study the mechanisms of chronic injury in heart allograft with chronic rejection.Methods:A model of cardiac chronic rejection in the rat based on tolerance induced through donor specific blood transfusions was used.The subpopulation and the distribution of infiltrating cells and the expression of adhesion molecule and growth factors were studied by immunohistochemistry and Northern blot analysis in the chronic rejection model.Results:Infiltrating cells were predominantly T lymphocytes and macrophages,mostly evident in the interstitial,subendocardial and perivascular areas.Allografts were demonstrated significantly elevated number of CD45+,CD4+,CD8+,TCR+,CD45RB+ cells,macrophages(ED_1) and NK cells at both 3 and 6 months compared with normal rat hearts and isografts at 3 months.Damaged areas also were observed expression of the adhesion molecules ICAM-1,LFA-1,basic fibroblast growth factor (bFGF) and transforming growth factor(TGF-β1).Northern blot analysis of total RNA,showed 5 to 6 fold upregulation of TGF-β1 mRNA in the chronic rejection model compared with normal rat hearts.Conclusion:These results suggest that T lymphocytes and macrophages play a central role in the development on chronic rejection and the increased expression of ICAM-1,LFA-1,bFGF and TGF-β1 in this model supports the involvement of these adhesion molecules and growth factors in the development of cardiac allograft vasculopaphy.
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2005年第7期508-512,共5页
Chinese Journal of Immunology
关键词
心脏移植
慢性排斥
细胞免疫
胞间黏附分子
生长因子
Heart transplantation
Chronic rejection
Cellular immunity
Adhesion molecules
Growth factors
