Maeda T, Marubayashi S, Fukuma K, Sugino K, Koyama S, Yamada K, Ito H, Dohi K
Second Department of Surgery, Hiroshima University School of Medicine, Japan.
Surg Today. 1997;27(1):22-9. doi: 10.1007/BF01366935.
We compared the therapeutic effects of anti-leukocyte adhesion molecule antibodies (mAbs), a nitric oxide (NO) synthase inhibitor (monomethyl-L-arginine, NMLA), and methylprednisolone (MP) on experimental endotoxin-induced shock in mice. Lipopolysaccharide (LPS, 30 mg/kg) was administered to ICR mice intraperitoneally, While 1 mg/kg mAb, 5-20 mg/kg NMLA, or 30 mg/kg MP was administered intravenously. The placebo group received phosphate-buffered saline. The survival rate of the placebo group 48 h after LPS injection was 36%. The administration of anti-CD11a, anti-CD18, anti-lectin cell adhesion molecule-1 (anti-LECAM-1), and MP increased the survival rate to 70, 62, 64, and 100%, respectively; however, NMLA had no significant effect. A FACS analysis revealed that the CD18 expression of granulocytes increased 12-fold within 30 min after LPS administration. MP significantly suppressed its expression. The plasma level of nitrate/nitrite increased from 20 to 260 and 1000 microM 4 and 16 h, respectively, 20 mg/kg NMLA abolished NO production at 4 h, while MP inhibited it for up to 16 h. The hepatic malondialdehyde level increased from 0.50 to 2.46 nmol/mg protein at 4 h. Administration of anti-CD18 and MP reduced the level to 1.80 and 1.41 nmol/mg protein, respectively, whereas NMLA did not affect it. The mAbs and MP were concluded to be useful agents for endotoxin shock. The abolition of NO production had little influence on the hepatic cellular injury associated with endotoxemia.
我们比较了抗白细胞粘附分子抗体（单克隆抗体）、一氧化氮（NO）合酶抑制剂（单甲基-L-精氨酸，NMLA）和甲基强的松龙（MP）对实验性内毒素诱导的小鼠休克的治疗效果。将脂多糖（LPS，30mg/kg）腹腔注射给ICR小鼠，同时将1mg/kg单克隆抗体、5-20mg/kg NMLA或30mg/kg MP静脉注射。安慰剂组接受磷酸盐缓冲盐水。LPS注射后48小时，安慰剂组的存活率为36%。给予抗CD11a、抗CD18、抗凝集素细胞粘附分子-1（抗LECAM-1）和MP后，存活率分别提高到70%、62%、64%和100%；然而，NMLA没有显著效果。流式细胞仪分析显示，LPS给药后30分钟内粒细胞的CD18表达增加了12倍。MP显著抑制了其表达。血浆硝酸盐/亚硝酸盐水平分别在4小时和16小时从20微摩尔增加到260微摩尔和1000微摩尔，20mg/kg NMLA在4小时消除了NO的产生，而MP在长达16小时内抑制了NO的产生。肝丙二醛水平在4小时时从0.50纳摩尔/毫克蛋白增加到2.46纳摩尔/毫克蛋白。给予抗CD18和MP后，水平分别降至1.80纳摩尔/毫克蛋白和1.41纳摩尔/毫克蛋白，而NMLA对此没有影响。得出结论，单克隆抗体和MP是治疗内毒素休克的有效药物。NO产生的消除对内毒素血症相关的肝细胞损伤影响很小。
