Htwe T, Suzuki M, Ouchi K, Fukuhara K, Matsuno S
First Department of Surgery, Tohoku University School of Medicine, Sendai, Japan.
J Surg Res. 1996 Feb 15;61(1):206-14. doi: 10.1006/jsre.1996.0106.
In gram-negative septicemia, endotoxin-induced free radicals probably damage the liver cells by membrane lipid peroxidation. Phosphotidylcholine hydroperoxide (PCOOH), a primary lipid peroxidation product can be applied as a parameter to measure the extent of liver damage. The protective effects of urinastatin and free radical scavengers, superoxide dismutase (SOD), and catalase against hepatic lipid peroxidation and tissue energy reserves in the liver during endotoxemia were evaluated in rats with gram-negative septicemia induced by cecal ligation and puncture (CLP). One hundred and sixty-five rats were divided into three groups. The first two groups consisted of 45 rats each. Group (1) was used for blood endotoxin level and liver function tests, group (2) for hepatic energy charge and PCOOH measurement, and group (3) (n = 75) for survival study. In each group, control animals received saline injection only. Urinastatin was injected twice intravenously through tail veins using 50,000 u/kg at 0 and 12 hr after CLP. SOD 90,000 u/kg and catalase 50,000 u/kg were given subcutaneously just before CLP and every 3 hr thereafter up to 24 hr. Liver and blood specimens were taken at time points 0, 12, and 24 hr after CLP. Increased concentration of PCOOH in liver denotes that endotoxemia can damage the liver by hepatocellular lipid peroxidation. Attenuation of lipid peroxidation, which correlated with liver enzyme leakage, was noted by finding significant decreased concentrations of PCOOH (P < 0.001), improvement in energy charge (P < 0.05), and survivability (P < 0.05) was seen in urinastatin or radical scavenger-treated groups. These results suggested that urinastatin has protective effect against free radical-induced lipid peroxidation probably by inhibiting proteases especially elastase, from polymorphonuclear leucocytes. SOD and catalase, which scavenged oxygen free radicals, also suppressed free radical-induced lipid peroxidation. Improvement in survivability was also seen in treated groups.
在革兰氏阴性菌败血症中，内毒素诱导产生的自由基可能通过膜脂质过氧化作用损害肝细胞。磷脂酰胆碱过氧化氢（PCOOH）作为脂质过氧化的主要产物，可用作衡量肝损伤程度的一个指标。在通过盲肠结扎和穿刺（CLP）诱导革兰氏阴性菌败血症的大鼠中，评估了乌司他丁以及自由基清除剂超氧化物歧化酶（SOD）和过氧化氢酶对内毒素血症期间肝脏脂质过氧化和肝脏组织能量储备的保护作用。165只大鼠被分为三组。前两组每组各有45只大鼠。第（1）组用于检测血内毒素水平和肝功能，第（2）组用于测量肝脏能量负荷和PCOOH，第（3）组（n = 75）用于生存研究。在每组中，对照动物仅接受生理盐水注射。在CLP后0小时和12小时，通过尾静脉给乌司他丁静脉注射两次，剂量为50000单位/千克。在CLP前皮下注射SOD 90000单位/千克和过氧化氢酶50000单位/千克，此后每3小时注射一次，直至24小时。在CLP后0小时、12小时和24小时采集肝脏和血液标本。肝脏中PCOOH浓度升高表明内毒素血症可通过肝细胞脂质过氧化作用损害肝脏。通过发现PCOOH浓度显著降低（P < 0.001）、能量负荷改善（P < 0.05）以及在乌司他丁或自由基清除剂处理组中观察到生存率提高（P < 0.05），注意到与肝酶泄漏相关的脂质过氧化作用减弱。这些结果表明，乌司他丁可能通过抑制多形核白细胞中的蛋白酶尤其是弹性蛋白酶，对自由基诱导的脂质过氧化具有保护作用。清除氧自由基的SOD和过氧化氢酶也抑制了自由基诱导的脂质过氧化。在处理组中也观察到了生存率的提高。
