White W L, Zhang Y L, Shelby J, Trautman M S, Perkins S L, Hammond E H, Shaddy R E
Department of Surgery, University of Utah School of Medicine, Salt Lake City, USA.
J Heart Lung Transplant. 1997 Feb;16(2):250-5.
Apoptosis has been implicated in myocardial reperfusion injury and in experimental transplantation rejection. One mechanism of apoptosis is through the interaction of the cell-surface Fas receptor on target cells and the Fas ligand that is expressed on cytotoxic T cells. The purpose of this study was to look for evidence of myocardial Fas receptor, Fas ligand, and apoptosis in a murine heterotopic heart transplantation model of chronic rejection/graft vasculopathy.
Using the nick-end labeling technique, we examined a murine heterotopic heart transplantation model of chronic rejection/graft vasculopathy (strain B10.A to B10.BR) histologically for evidence of DNA fragmentation. MRNA for the Fas receptor, Fas ligand, and beta-actin was detected with reverse transcription-polymerase chain reaction.
Hearts harvested after 30 and 60 days showed an intimal index of the allografts (0.5 +/- 0.1) (mean +/- standard error) that was at least five times more than syngeneic grafts and native (nontransplanted) hearts (p < 0.01). In situ nick end-labeling of partially degraded DNA with terminal deoxynucleotydil transferase showed an increase in apoptotic cells in allografts and syngeneic grafts compared with native hearts. Reverse transcription-polymerase chain reaction detected equal myocardial RNA signal intensity of Fas receptor and beta-actin in allografts, syngeneic grafts, and native hearts. In contrast, allografts showed a strong signal for the Fas ligand mRNA, a signal not seen in syngeneic grafts or native hearts.
Apoptosis is occurring in both allografts and syngeneic grafts in this murine model of chronic rejection/graft vasculopathy, although distinct mechanisms may be involved.
细胞凋亡与心肌再灌注损伤及实验性移植排斥反应有关。细胞凋亡的一种机制是通过靶细胞表面的Fas受体与细胞毒性T细胞上表达的Fas配体相互作用。本研究的目的是在慢性排斥/移植血管病的小鼠异位心脏移植模型中寻找心肌Fas受体、Fas配体和细胞凋亡的证据。
我们使用缺口末端标记技术，对慢性排斥/移植血管病（B10.A品系至B10.BR品系）的小鼠异位心脏移植模型进行组织学检查，以寻找DNA片段化的证据。通过逆转录-聚合酶链反应检测Fas受体、Fas配体和β-肌动蛋白的mRNA。
30天和60天后采集的心脏显示，同种异体移植物的内膜指数为（0.5±0.1）（平均值±标准误），至少是同基因移植物和天然（未移植）心脏的五倍（p<0.01）。用末端脱氧核苷酸转移酶对部分降解的DNA进行原位缺口末端标记显示，与天然心脏相比，同种异体移植物和同基因移植物中的凋亡细胞增加。逆转录-聚合酶链反应检测到同种异体移植物、同基因移植物和天然心脏中Fas受体和β-肌动蛋白的心肌RNA信号强度相等。相比之下，同种异体移植物显示出Fas配体mRNA的强信号，而同基因移植物或天然心脏中未观察到该信号。
在这个慢性排斥/移植血管病的小鼠模型中，同种异体移植物和同基因移植物中均发生了细胞凋亡，尽管可能涉及不同的机制。
