Bilzer M, Witthaut R, Paumgartner G, Gerbes A L
Department of Medicine II, Klinikum Grosshadern, University of Munich, Germany.
Gastroenterology. 1994 Jan;106(1):143-51. doi: 10.1016/s0016-5085(94)94961-1.
BACKGROUND/AIMS: Atrial natriuretic peptide (ANP) protects against hypoxia/reoxygenation-induced damage of cultured hepatocytes, thus suggesting a therapeutic potential in the liver. Therefore, the effects of ANP on hepatic ischemia/reperfusion injury after warm ischemia were studied.
Livers of male Sprague-Dawley rats subjected to 60 minutes of warm ischemia at 37 degrees C were perfused in the presence or absence of 200 and 20 nmol/L ANP.
Sinusoidal lactate dehydrogenase efflux increased to 2000 +/- 264 and 126 +/- 50 mU.min-1.g liver-1 after 1 minute and 60 minutes of reperfusion, but it only increased to 1240 +/- 160 and 22 +/- 16 mU.min-1.g liver-1 in the presence of 200 nmol/L ANP during the preischemic and postischemic perfusion period. The postischemic bile flow (0.67 +/- 0.18 microL.min-1.g liver-1) was significantly improved with 200 nmol/L ANP (0.92 +/- 0.05) and showed a linear correlation to biliary glutathione excretion. In contrast, 20 nmol/L ANP had no protective effects. Administration of 200 nmol/L ANP during the preischemic perfusion period alone (but not after starting reperfusion) markedly preserved postischemic liver function.
Continuous ANP administration or ANP pretreatment alone prevents hepatic ischemia/reperfusion injury, possibly because of influences on intracellular signal transduction processes. The correlation between bile flow and biliary glutathione excretion supports the hypothesis that biliary glutathione transport is one of the osmotic driving forces in postischemic bile formation.
背景/目的：心房利钠肽（ANP）可保护培养的肝细胞免受缺氧/复氧诱导的损伤，因此提示其在肝脏具有治疗潜力。因此，研究了ANP对热缺血后肝缺血/再灌注损伤的影响。
对雄性Sprague-Dawley大鼠的肝脏在37℃下进行60分钟热缺血，在有或无200和20 nmol/L ANP的情况下进行灌注。
再灌注1分钟和60分钟后，肝窦乳酸脱氢酶流出量分别增加至2000±264和126±50 mU·min-1·g肝脏-1，但在缺血前和缺血后灌注期存在200 nmol/L ANP时，仅分别增加至1240±160和22±16 mU·min-1·g肝脏-1。200 nmol/L ANP可使缺血后胆汁流量（0.67±0.18 μL·min-1·g肝脏-1）显著改善（0.92±0.05），并与胆汁谷胱甘肽排泄呈线性相关。相比之下，20 nmol/L ANP无保护作用。仅在缺血前灌注期（而非开始再灌注后）给予200 nmol/L ANP可显著保护缺血后肝功能。
持续给予ANP或单独进行ANP预处理可预防肝缺血/再灌注损伤，可能是因为其对细胞内信号转导过程的影响。胆汁流量与胆汁谷胱甘肽排泄之间的相关性支持了胆汁谷胱甘肽转运是缺血后胆汁形成中渗透驱动力之一的假说。
