Arai Masahiro, Tejima Kazuaki, Ikeda Hitoshi, Tomiya Tomoaki, Yanase Mikio, Inoue Yukiko, Nagashima Kayo, Nishikawa Takako, Watanabe Naoko, Omata Masao, Fujiwara Kenji
Department of Gastroenterology, Toshiba General Hospital, Shinagawa-ku, Tokyo, Japan.
J Gastroenterol Hepatol. 2007 Jun;22 Suppl 1:S65-7. doi: 10.1111/j.1440-1746.2006.04656.x.
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.
短暂的组织缺血期可使组织对长时间缺血和再灌注产生抵抗，这一现象称为缺血预处理。在大鼠热缺血-再灌注模型中研究了缺血预处理的机制以及缺血预处理对肝再生的影响。缺血预处理可减轻热缺血-再灌注后的肝损伤，而枯否细胞清除可逆转这一作用。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作用，用亚致死剂量的过氧化氢预处理可模拟缺血预处理的效果。对大鼠肝脏进行缺血预处理，然后进行70%的部分肝切除术。随后连续评估肝再生情况。缺血预处理促进肝再生，腺苷A2受体拮抗可逆转这一作用，腺苷A2受体激动则可模拟这一作用。缺血预处理和腺苷A2受体激动对肝再生的促进作用可被枯否细胞清除所逆转。总之，缺血预处理刺激枯否细胞产生活性氧，从而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中的腺苷A2受体途径促进肝再生。
