Ischemic preconditioning in liver pathophysiology
Ischemic preconditioning in liver pathophysiology
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DOI：
10.1111/j.1440-1746.2006.04656.x
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发表时间：
2007-06-01
影响因子：
4.1
通讯作者：
Fujiwara, Kenji
中科院分区：
文献类型：
--
作者：
Arai, Masahiro;Tejima, Kazuaki;Fujiwara, Kenji
短暂的组织缺血会产生组织对长时间缺血和再灌注的抵抗力，这种现象称为缺血预处理。采用大鼠热缺血再灌注模型研究缺血预处理的作用机制及其对肝再生的影响。缺血预处理可减轻热缺血再灌注后肝脏的损伤，且这种作用可被枯否细胞耗竭逆转。缺血预处理刺激枯否细胞产生活性氧。活性氧清除剂可逆转缺血预处理的效应，亚致死剂量过氧化氢预处理可模拟缺血预处理的效应。大鼠肝脏缺血预处理，并进行70%的部分肝切除术。然后连续评价肝再生。缺血预处理促进肝再生，这是逆转腺苷A2受体拮抗剂和腺苷A2受体激动剂模拟。枯否细胞耗竭可逆转缺血预处理和腺苷A2受体激动对肝再生的促进作用。结论：缺血预处理可刺激枯否细胞产生活性氧，保护肝细胞免受热缺血再灌注损伤;缺血预处理通过枯否细胞腺苷A2受体途径促进肝再生。
Brief periods of tissue ischemia produced tissue resistance to prolonged ischemia and reperfusion, a phenomenon called ischemic preconditioning. The mechanisms of ischemic preconditioning were examined in a rat warm ischemia-reperfusion model as well as the effect of ischemic preconditioning on liver regeneration. Ischemic preconditioning decreased liver injury after warm ischemia-reperfusion, which was reversed by Kupffer cell depletion. Ischemic preconditioning stimulated Kupffer cells to produce reactive oxygen species. Scavengers of reactive oxygen species reversed the effect of ischemic preconditioning, and pretreatment with sublethal dose of hydrogen peroxide mimicked ischemic preconditioning effect. Rat livers were preconditioned by ischemia and subjected to 70% partial hepatectomy. Liver regeneration was then evaluated serially. Ischemic preconditioning promoted liver regeneration, which was reversed by adenosine A2 receptor antagonism and mimicked by adenosine A2 receptor agonism. Promotion of liver regeneration by ischemic preconditioning and adenosine A2 receptor agonism were reversed by Kupffer cell depletion. In conclusion, ischemic preconditioning stimulates Kupffer cells to produce reactive oxygen species, leading to hepatocyte protection against warm ischemia-reperfusion injury; and ischemic preconditioning promoted liver regeneration via adenosine A2 receptor pathway in Kupffer cells.