Induction of Different Types of Cell Death After Normothermic Liver Ischemia-Reperfusion
Induction of Different Types of Cell Death After Normothermic Liver Ischemia-Reperfusion
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DOI：
10.1016/j.transproceed.2010.09.140
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发表时间：
2010-12-01
影响因子：
0.9
通讯作者：
Gugenheim, J.
中科院分区：
文献类型：
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作者：
Cursio, R.;Colosetti, P.;Gugenheim, J.
正常肝缺血再灌注（I-R）可诱导肝细胞自噬、凋亡和坏死。本研究的目的是探讨这三种类型的细胞死亡的正常肝I-R大鼠。肝段性常温缺血120分钟。通过透射电镜和LC3（轻链3）免疫组化研究评估肝自噬。通过FLIVO（体内荧光）和TUNEL （tdt介导的dUTP缺口末端标记）检测肝细胞凋亡。光镜检查确定肝坏死。与非缺血肝叶相比，缺血肝叶在再灌注后6小时自噬增加。荧光显微镜显示，与非缺血肝叶相比，缺血肝叶再灌注6小时后原位caspase-3和-7特异性活性增加。TUNEL法对凋亡细胞的定量分析显示，再灌注后6小时，缺血肝叶与非缺血肝叶相比明显增加。再灌注后6小时，缺血肝叶坏死细胞死亡率明显高于非缺血肝叶（P < 0.005）。总之，120分钟的正常肝脏I-R导致自噬、凋亡和坏死细胞死亡增加。
Normothermic liver ischemia-reperfusion (I-R) may induce hepatocellular autophagy, apoptosis, and necrosis. The aim of this study was to investigate these three types of cell death in normothermic liver I-R in rats. A segmental normothermic ischemia of the liver was induced for 120 minutes. Liver autophagy was evaluated by transmission electron microscopy and LC3 (Light Chain 3) immunohistochemical studies. Liver apoptosis was assessed by FLIVO (FLuorescence in vIVO) and TUNEL (TdT-mediated dUTP nick end labeling) assays. Liver necrosis was determined by optical microscopic examination. Autophagy was increased in ischemic liver lobes at 6 hours after reperfusion, compared with nonischemic lobes. Fluorescence microscopy showed in situ caspase-3 and -7 specific activity to be increased in ischemic liver lobes after 6 hours of reperfusion, compared with nonischemic lobes. Quantitative analysis of apoptotic cells evaluated by the TUNEL method showed a clearly significant increase in ischemic liver lobes at 6 hours after reperfusion, compared with nonischemic lobes. Necrotic cell death was significantly increased in ischemic liver lobes at 6 hours after reperfusion, compared with nonischemic lobes (P < .005). In conclusion, 120 minutes normothermic liver I-R resulted in increased autophagic, apoptotic and necrotic cell death.