Niu X, Arthur P G, Jeffrey G P
School of Medicine and Pharmacology University of Western Australia, Crawley, Western Australia.
Transplant Proc. 2010 Jun;42(5):1563-8. doi: 10.1016/j.transproceed.2010.03.143.
Iron chelators and antioxidants have been shown to prevent hypothermia-induced apoptosis in hepatocytes. This study examined whether iron chelation and antioxidants could also prevent hypothermia-induced necrosis. Isolated rat hepatocytes were incubated at 4 degrees C for 6 hours and then rewarmed at 37 degrees C for 18 hours with or without the iron chelator deferoxamine and a selection of antioxidants. There was no evidence of increased cell death or adenosine triphosphate depletion during hypothermic incubation. After hypothermia and rewarming, the majority of rat hepatocytes died of necrosis as indicated by the absence of DNA fragmentation, caspase 3 activity, and apoptotic bodies. Cell death was significantly reduced if deferoxamine or a selection of antioxidants were present during hypothermia and rewarming. Deferoxamine was more effective in preventing cell death when added prior to hypothermia, indicating cell death processes were likely initiated during hypothermia.
铁螯合剂和抗氧化剂已被证明可预防低温诱导的肝细胞凋亡。本研究检测了铁螯合和抗氧化剂是否也能预防低温诱导的坏死。将分离的大鼠肝细胞在4℃孵育6小时,然后在有或没有铁螯合剂去铁胺和多种抗氧化剂的情况下于37℃复温18小时。在低温孵育期间,没有细胞死亡增加或三磷酸腺苷消耗的证据。低温和复温后,大多数大鼠肝细胞死于坏死,这表现为无DNA片段化、半胱天冬酶3活性和凋亡小体。如果在低温和复温期间存在去铁胺或多种抗氧化剂,则细胞死亡显著减少。在低温前添加去铁胺在预防细胞死亡方面更有效,表明细胞死亡过程可能在低温期间启动。