内源性应激损伤对移植后大鼠心脏病变的影响(英文)

Endogenous stress contributes to cardiac injury after heart transplantation in rats

目的:应激效应在多种心脏疾病的发生、发展中发挥重要作用。本研究探讨在心脏移植后慢性排斥反应期,是否存在应激效应对心肌和冠状动脉的损伤。方法:采用Ono模型建立大鼠心脏移植,采用蛋白质组技术比较同基因移植与异基因移植后2周、8周左室心脏组织的蛋白质变化,通过基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)分析获得肽质量指纹图谱,经Matrix Science查询软件搜索获得匹配的蛋白质。结果:异基因移植心脏在术后2周即出现血管内膜增厚[(2.07%±0.93%)vs.(27.58%±11.14%),P<0.01)],在术后8周更明显[(2.34%±1.06%)vs.(72.29%±20.57%),P<0.01)];蛋白质组学技术分析左室心肌,发现了45个差异表达的蛋白质;通过数据库鉴定得到37种蛋白质,其中9个与应激和损伤相关蛋白质,进一步使用Western印迹验证了其中的2个。结论:移植后心肌持续受到应激效应的损伤可能是大鼠心脏移植后冠状动脉病变发生发展的一个重要原因。

Objective Stress effect plays an important role in the development of some myocardial diseases.We hypothesized it was important nosogenesis to myocardial damage and cardiac allograft vasculopathy.Methods The transplanted hearts from Lewis to Wister rats served as allografts and from Lewis to Lewis rats as isografts based Ono＇s model.The differential proteins in the transplanted hearts were separated by comparative proteome,and then identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry（MALDI-TOF-MS） and searched by Matrix Science software system.Results All transplanted hearts were characterized by lumen loss [（total vessel area-luminal area）/total vessel area] in the coronary artery 2 weeks after the operation [（2.07%±0.93%） vs.（27.58%±11.14%）,P〈0.01],but more predominant after 8 weeks [（2.34%±1.06%） vs.（72.29%±20.57%）,P〈0.01].All samples of the left ventricle were analyzed by proteomic techniques and 37 distinct proteins involving their respective isoforms and subunits were identified.Nine proteins were correlated to endoplasmic reticulum stress effect and myocardial damage,and 2 proteins were verified by Western blot.Conclusion Stress plays an important role in cardiac allograft damage and the development of rat cardiac allograft vasculopathy.