Role of oxidative stress and microcirculatory disturbances in the liver injury.

通过体内实验模型和大鼠肝脏灌流模型研究氧化应激和微循环障碍的致病作用。为此，使用了活体荧光显微镜，辅以超灵敏相机和各种荧光探针。缺血再灌注损伤始于肝小叶中段，并延伸至中心周区。这种作用可被黄嘌呤氧化酶抑制剂和前列腺素E_1抑制。用荧光标记的红细胞显示急性乙醇中毒时的微循环障碍，在高浓度乙醇时不显示微循环障碍。肝脏小叶中心区NADH在体内和肝脏灌流中也有增加。内毒素性肝损伤是由枯否细胞释放一氧化氮引起的线粒体功能障碍所致。此作用可被一氧化氮合酶抑制剂L和一氧化氮合酶抑制剂阻断。在这些实验性肝损伤中，氧化应激和微循环障碍在发病机制中起着重要作用。

Pathogenetical role of oxidative stress and microcirculatory disturbances were investigated by experimental model in vivo and in perfused rat liver. To that effect, intravital fluorescence microscopy assisted by ultrasensitive camera and various fluorescence probes were used. Ischemica reperfusion injury was demonstrated to star from midzone of the hepatic lobule and extended to pericentral area. This was inhibited by xanthine oxidase inhibitor and prostagrandin E1. Microcirculatory disturbances in acute ethanol intoxication was demonstrated with fluorescence labeled RBC,at high ethanol concentration but not at low ethanol concentration. Increase of hepatic NADH in centrilobular area was also demonstrated in vivo as well as perfused liver. Endotoxin induced liver injury was demonstrated to be mediated by mitochondrial dysfunction by the release of nitric oxide from Kupffer cell. This was blocked by NO inhibitor such as L-NMMA and i-NOS inhibitor. In these experimental hepatic injury, oxidative stress and microcirculatory disturbances playd an important role in pathogenesis.