Development of perioperative management for hepatic resection based on the stellate cell function

1)硫氧还蛋白与星状细胞功能的关系：硫氧还蛋白是一种小分子氧化还原活性蛋白，具有抗氧化和抗凋亡作用。我们研究了硫氧还蛋白对肝纤维化的保护作用。硫代乙酰胺诱导的肝纤维化大鼠肝细胞中内源性硫氧还蛋白的诱导明显。过表达硫氧还蛋白可抑制肿瘤坏死因子-α诱导的HepG 2细胞死亡。与野生型小鼠相比，硫代乙酰胺诱导的肝纤维化和丙二醛在肝脏中的积累在转基因小鼠中受到抑制。从转基因小鼠中分离的肝星状细胞的增殖性低于从野生型小鼠中分离的肝星状细胞。重组硫氧还蛋白显著抑制血清或PDGF-BB刺激下原代培养的星状细胞的DNA合成。硫氧还蛋白未能控制培养的星状细胞胶原基因的表达。硫氧还蛋白可能通过抑制肝细胞增殖来控制肝纤维化 ...更多信息 e死亡、星状细胞增殖和氧化应激。2）肝微循环和Rock/Rho激酶抑制剂，Y-27632：Rock/Rho激酶抑制剂，Y-27632也已知防止肝星状细胞的活化和防止纤维化。我们在大鼠肝脏缺血/再灌注模型上采用半侧钳夹法研究了这一点。通过活体显微镜观察，Y-27632通过显著改善肝脏微循环来保护肝脏缺血/再灌注损伤。与假手术组相比，窦状静脉和窦后小静脉的直径、窦状静脉灌注率维持不变。白细胞在窦状隙和窦后小静脉中的粘附少得多，这也导致对血流障碍的保护。Y-27632还表现出改善内毒素血症引起的微循环障碍。3）NAC（N-乙酰半胱氨酸）对临床术后肝功能衰竭的影响：NAC（N-乙酰半胱氨酸）被给予1例术后高胆红素血症患者。肠内给予NAC后，血清胆红素水平有下降趋势。少

1)Relationship between thioredoxin and stellate cell function : Thioredoxin is a small redox-active protein with anti-oxidant and anti-apoptotic effect. We have investigated the protective effect of thioredoxin for hepatic fibrosis. Induction of endogenous thioredoxin was obvious in hepatocytes of thioacetamide-induced fibrotic liver of rats. Overexpression of thioredoxin inhibited tumor necrosis factor-(x-induced death of HepG2 cells. Thioacetamide-induced fibrosis and accumulation of malondialdehyde in the liver was suppressed in transgenic mice as compared with wild-type mice. Hepatic stellate cells isolated from transgenic mice was less proliferative than those isolated from wild type mice. Recombinant thioredoxin significantly inhibited DNA synthesis of primary-cultured stellate cells under serum or PDGF-BB stimulation. Thioredoxin failed to control collagen gene expression in cultured stellate cells. Thioredoxin has a potential to control hepatic fibrosis via inhibiting hepatocyt … More e death, proliferation of stellate cells and oxidative stress.2)Hepatic microcirculation and Rock/Rho kinase inhibitor, Y-27632 : Rock/Rho kinase inhibitor, Y-27632 is also known to prevent activation of hepatic stellate cell and prevent fibrosis. We have investigated it in ischemia/reperfusion model of rat liver using hemi-lateral clamp of the liver. Y-27632 protected ischemia/reperfusion-induced injury of the liver through remarkable improvement of hepatic microcirculation, which was observed by intravital microscopy. Diameter of sinusoid and postsinusoidal venule, sinusoidal perfusion rate were maintained as compared to sham group. Adherence of leucocytes in the sinusoid and postsinusoidal venule was much less, which results also in protection of disturbance of the blood flow. Y-27632 also exhibited to improve disturbance of microcirculation due to endotoxemia.3)Effect of NAC (N-acetylcisteine) on clinical postoperative liver failure : NAC (N-acetylcisteine) was administered to a posthepatectomized patient with hyperbilirubinemia. Serum bilirubin level tended to decreased after enteral administration of NAC. Less