【作者】 黄凯；

【导师】 陈龙；

【作者基本信息】 福建医科大学 ， 外科学， 2006， 硕士

【摘要】 目的缺血再灌注所致肺损伤是早期肺移植患者死亡和移植失败的主要原因,缺血再灌注损伤与细胞凋亡密切相关,而半胱天冬氨酸蛋白酶(caspase)是执行细胞凋亡的蛋白酶家族,在凋亡过程中发挥关键作用,通过抑制caspase有望消除肺移植再灌注后的细胞凋亡及改善缺血再灌注损伤,保护肺功能。本实验建立大鼠左肺原位移植缺血再灌注损伤动物模型,供肺保存液中加入caspase抑制剂Z-VAD-FMK,观察对移植肺缺血再灌注性细胞凋亡的影响,探索caspase抑制剂在肺移植中对供体肺的保护作用,以求减少术后肺缺血再灌注损伤,为临床上肺移植提供实验依据。方法以三袖套吻合技术建立大鼠左肺原位移植缺血再灌注损伤模型,进行30对大鼠左肺原位移植,随机分为2组:A组,对照组(n=15),以SD大鼠为供、受体;取出供肺并于4℃HTK液冷藏6小时后行肺移植。B组,实验组(n=15),以SD大鼠为供、受鼠,同A组取出供肺并于4℃HTK液冷藏6小时(此组HTK液中加入caspase抑制剂Z-VAD-FMK浓度为25μΜ)后行肺移植。肺移植再灌注后2小时取出移植肺,H-E染色光镜观测肺组织病理变化及电镜观察检测细胞形态学变化,应用TUNEL法检测肺泡细胞的凋亡情况,并测定肺的湿干重比值。结果1.肺再灌注后2小时,肺组织H-E染色可见肺泡细胞肿胀,肺泡间质水肿、增厚,肺泡腔渗出,及中性粒细胞浸润和肺泡结构破坏。更多还原

【Abstract】 ObjectiveIschemia-reperfusion-induced lung injury may lead to primary graft failure and remain a significant cause of morbidity and mortality after lung transplantation. Ischemia-reperfusion lung injury is associated with apoptotic cell death. Caspase are the key executioners of apoptosis. We hypothesized that caspase inhibitor might inhibit apoptosis and protect lung from IR injury. To establish rat orthotopic left pulmonary transplantation by the“cuff-like”vessel anastomosis technique, to observe the dynamic changes of alveolar apoptosis in ischemia-reperfusion induced pulmonary injury, to evaluate the protective effect of caspase inhibitor Z-VAD-FMK on lung ischemia-reperfusion injury after transplantation in rats. The purpose of this study was to investigate whether caspase inhibitor is effective in reducing lung ischemia-reperfusion injury.MethodsWe established rat orthotopic left pulmonary transplantation, in which the anastomosis of pulmonary artery, vein and bronchus was performed by using the cuff technique . 60 rats were randomly divided into two groups:GroupA(n=15): male SD rats underwent left lung transplantation with isografts from SD rats(Donor lungs stored in 40 ml of 4℃HTK for a period of 6 h cold ischemic storage time). GroupB(n=15): male SD rats underwent left lung transplantation with isografts from SD rats(Donor lungs stored in 40 ml of 4℃HTK and 25μΜcaspase inhibitor Z-VAD-FMK更多还原