Research for pathophysiology and therapeutic means of hepatic oxidatiye stress in obstructive iaundice.

为探讨氧化应激是否参与梗阻性黄疸合并手术应激的病理生理机制，采用胆总管结扎法建立梗阻性黄疸大鼠模型。腹腔注射5%葡萄糖或N-乙酰半胱氨酸（NAC）2周。胆管结扎后2周，经股静脉给予脂多糖。脂多糖给药后2小时，NAC组的谷胱甘肽-S-转移酶（肝细胞损伤的可靠标志物）血清浓度显著高于5%葡萄糖组。NAC组肝细胞胞浆还原型谷胱甘肽（GSH）浓度显著高于5%葡萄糖组。NAC组肝细胞胞浆中氧化型谷胱甘肽（GSSG）浓度显著低于5%葡萄糖组。线粒体GSSG ...更多信息 /GSH值是线粒体氧化应激的标志物，NAC组低于5%葡萄糖组。NAC组肝组织标本中三磷酸腺苷浓度显著高于5%葡萄糖组。采用淘析器获得浸润至肝组织的中性粒细胞，并采用流式细胞术分析中性粒细胞氧化应激。NAC组肝细胞氧化应激水平明显低于5%葡萄糖组，说明NAC能明显减轻梗阻性黄疸合并内毒素休克时肝细胞的损伤和肝脏的氧化应激水平，并观察了NAC对梗阻性黄疸合并内毒素休克犬肝脏血流动力学的影响。梗阻性黄疸和内毒素血症犬门静脉血流量和肝微循环组织血流量较正常犬减少。NAC显著增加门静脉血流量和肝微循环组织血流量。因此，NAC可改善梗阻性黄疸合并内毒素血症犬的肝脏血流动力学。少

The aim of the present research was to investigate whether oxidative stress involves in pathophysiologic causes of animals with obstructive jaundice complicating surgical stress.A cholestatic rat model was produced with ligation of the common bile duct ligation for 2 weeks. Either 5% glucose or N-acetylcysteine (NAC) was administered into abdominal cavity for 2 weeks. Two weeks after bile duct ligation, lipopolysaccharide was administered through the femoral vein. Two hours after administration of lipopolysaccharide, serum concentration of glutathione-S-transferase, which is a reliable marker of hepatocellular injury, was significantly higher in the NAC group than in the 5% glucosegroup. Hepatocellular cytoplasmic concentration of reduced glutathione (GSH) was significantly higher in the NAC group than in the 5% glucose group. Hepatocellular cytoplasmic concentration of oxidized glutathione (GSSG) was significantly lower in the NAC group than in the 5% glucose group. Mitochondrial GSSG … More /GSH value, which is a marker of mitochondrial oxidative stress, was lower in the NAC group than in the 5% glucose group. Concentration of adenosine triphosphate in specimens of liver tissue was significantly higher in the NAC group than in the 5% glucose group. Neutrophils infiltrating to liver tissue was obtained using elutriator and neutrophil oxidative stress was measured with flow cytometric analysis. Neutrophil oxidative stress was lower in the NAC group than in the 5% glucose group.In conclusion, NAC significantly reduced hepatocellular injury and hepatic oxidative stress in the animals with obstructive jaundice complicating endotoxin shock.The effects of NAC on hepatic hemodynamics were investigated in dogs with obstructive jaundice complicating endotoxin shock. In dogs with obstructive jaundice and endotoxicemia, portal flow volume and hepatic microcirculatory tissue flow were reduced as compared with normal dogs. NAC significantly increased portal flow volume and hepatic microcirculatory tissue flow volume. Therefore, NAC can improve hepatic hemodynamics in dogs with obstructive jaundice complicating endotoxicemia. Less