外源性一氧化碳释放分子2对严重烧伤小鼠肝脏炎性反应的抑制作用

目的 观察外源性一氧化碳释放分子2（CORM-2）对严重烧伤小鼠肝脏炎性反应的抑制作用，并探讨其机制。方法 将C57BL／6小鼠随机分成假伤组（模拟烧伤）、假伤＋CORM-2组、烧伤组、烧伤＋CORM-2组及烧伤＋二甲亚砜（DMSO）组，每组9只。假伤＋CORM-2组除伤后使用CORM-2以外，其他处理同假伤组。烧伤＋CORM-2组及烧伤＋DMSO组除伤后分别使用CORM-2、DMSO外，其余处理同烧伤组。于伤后24h检测小鼠血清丙氨酸转氨酶（ALT）及天冬氨酸转氨酶（AST）的水平，肝组织髓过氧化物酶（MPO）及核因子KB（NF-kB）活性，胞间黏附分子1（ICAM-1）和血管细胞黏附分子1（VCAM-1）蛋白的表达；检测各组小鼠肝窦内皮细胞（HSEC）经各自血清刺激后对中性粒细胞（PMN）的黏附作用。结果 与假伤组比较，烧伤组小鼠血清ALT、AST的水平[（398±34）、（122±22）U／L]及肝组织MPO活性、肝组织ICAM-1和VCAM-1蛋白表达水平均明显升高（P〈0．05或P〈0．01）。与烧伤组比较，烧伤＋CORM-2组上述情况明显改善，且NF-kB活性下降。与假伤组比较，烧伤组小鼠HSEC对PMN的黏附作用增强；烧伤＋CORM-2组该作用明显弱于烧伤组（P〈0．05）。结论 外源性CORM-2能明显抑制肝组织NF-kB活性，减少ICAM-l、VCAM-l蛋白的表达水平，减轻严重烧伤后组织中白细胞滞留，改善肝功能，可有效减轻肝脏炎性反应。

The inhibitory effects of extrinsic carbon monoxide-releasing molecules Ⅱ on inflammatory responses in liver of mice with severe burns

OBJECTIVE: To investigate the inhibitory effects of extrinsic carbon monoxide-releasing molecules II on inflammatory responses in liver of mice with severe burns and its potential mechanisms. METHODS: Forty-five male C57BL/6 mice were randomly divided into sham (simulation of burn with 37 degrees C warm water), sham + CORM-2 (with 8 mg/kg CROM-2 after the same manipulation as sham group), burn (with 15% TBSA full-thickness burns), burn + CORM-2 (with 8 mg/kg CROM-2 after the same manipulation as burn group), burn + DMSO (with DMSO after the same treatment as burn group) groups,with 9 mice in each group. The serum level of ALT and AST were determined at 24 post-burn hours (PBH), and the level of myeloperoxidase (MPO), nuclear factor (NF) kappaB, intercellular adhesion molecular (ICAM-1), vascular cell adhesion molecular (VCAM-1), as well as adhesion of polymorphonuclear leucocytes to sinusoidal endothelial cells (HSECs) after serum stimulation were detected and assessed at the same time-points. RESULTS: The level of ALT and AST (398 +/- 34,122 +/- 22 ), the activity of MPO and NF-kappaB, the protein level of ICAM-1 and VCAM-1 in burn group were obviously increased when compared with those in sham group and burn + CROM-2 group (P < 0.05 or P < 0.01). Additionally, the adhesion of PMN on HSEC after stimulation of serum in burn group was enhanced, while it was markedly inhibited after stimulation of serum in burn + CORM-2 group (P < 0.05). CONCLUSION: Extrinsic CORM-2 exhibits the ability to inhibit NF-kappaB activity, reduces the hepatic expression of ICAM-1 and VCAM-1, thereby alleviating sequestration of leukocytes after severe burns, so that hepatic inflammatory response is ameliorated, and liver function is improved.