Heme oxygenase-1 overexpression protects rat livers from ischemia/reperfusion injury with extended cold preservation
Heme oxygenase-1 overexpression protects rat livers from ischemia/reperfusion injury with extended cold preservation
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DOI：
10.1034/j.1600-6143.2001.001002121.x
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发表时间：
2001-07-01
影响因子：
8.8
通讯作者：
Kupiec-Weglinski, JW
中科院分区：
文献类型：
--
作者：
Kato, H;Amersi, F;Kupiec-Weglinski, JW
本研究探讨血红素氧合酶-1（HO-1）介导的细胞保护作用及其机制。在第一组中，大鼠分别用钴原卟啉（CoPP）或锌原卟啉（ZnPP）、HO-1诱导剂和拮抗剂预处理。肝脏在4 ℃下保存24小时，然后离体灌注2小时。与ZnPP组相比，用CoPP预处理的肝脏具有显著更高的门静脉血流量和增加的总胆汁产量。这与肝细胞损伤/肝功能的组织学（Banff）标准相关。在第二组中，将大鼠肝脏在4 ℃下保存24小时或40小时，然后移植到同基因受体中。保存24小时后，80%的大鼠携带CoPP预处理的肝移植物存活21天（对照组为50%）。冷保存40小时后，CoPP组第1、7和21天的肝移植存活率分别为：100%、71%和57%（对照组为50%、50%和33%）。这与浸润性巨噬细胞HO-1过表达（免疫组织学/蛋白质印迹）后肝细胞损伤的肝功能/组织学（Suzuki）标准改善相关。本研究记录了HO-1诱导剂在预防肝移植物长期储存引起的缺血/再灌注损伤中的潜在效用。
This study analyzes the effects and mechanisms of heme oxygenase-1 (HO-1)-mediated cytoprotection in rat livers exposed to cold preservation. In the first series, rats were pretreated with cobalt protoporphyrin (CoPP) or zinc protoporphyrin (ZnPP), HO-1 inducer and antagonist, respectively. Livers were stored at 4degreesC for 24h, and then perfused ex vivo for 2h. Livers pretreated with CoPP had significantly higher portal venous blood flow and increased total bile production, as compared with the ZnPP group. This correlated with histologic (Banff) criteria of hepatocyte injury/liver function. In the second series, rat livers were stored at 4degreesC for 24 h or 40 h, and then transplanted into syngeneic recipients. After 24h of preservation, 80% of rats bearing CoPP-pretreated liver grafts survived 21 days (vs. 50% in controls). After 40h of cold preservation, liver transplant survival at day 1, 7 and 21 for the CoPP group was: 100%, 71% and 57%, respectively (vs. 50%, 50% and 33% in controls). This correlated with Improved hepatic function/histologic (Suzuki) criteria of hepatocyte injury after HO-1 overexpression (immunohistology/Western blots) by infiltrating macrophages. This study documents the potential utility of HO-1-inducing agents In preventing ischemia/reperfusion injury resulting from prolonged storage of liver transplants.