Sun Bing-Wei, Sun Yan, Sun Zhi-Wei, Chen Xi
Department of Burns and Plastic Surgery, Affiliated Hospital, Jiangsu University, 438 Jiefang Rd. Zhenjiang 212001, Jiangsu Province, China.
World J Gastroenterol. 2008 Jan 28;14(4):547-53. doi: 10.3748/wjg.14.547.
To explore the effects of CO-releasing molecules [tricarbonyldichlororuthenium (II) dimer, CORM-2]-liberated CO on attenuation of inflammatory responses in liver of an experimental animal model of thermal injury and to investigate the associated potential mechanisms.
Thirty-six mice were assigned to three groups in three respective experiments. In each experiment, mice in sham group (n=4) received sham thermal injury, whereas mice in burn group (n=4) received a 15% of total body surface area (TBSA) full-thickness thermal injury, and mice in burn+CORM-2 group (n=4) received the same thermal injury with immediate administration of CORM-2 (8 mg/kg, iv). Hepatic tissue sections were stained with hematoxylin and eosin and examined under a light microscope. Levels of aminotransferases (ALT and AST) and nitric oxide (NO) were measured by biochemical methods. Tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL-1beta) activity, and the protein expression of iNOS and HO-1 in serum and tissue homogenates were assessed. In in vitro experiments, Kupffer cells were stimulated with LPS (10 microg/mL) for 4 h in the presence or absence of CORM-2 (10-100 micromol/L). Subsequently, the expression levels of TNF-alpha and NO production were assessed.
Pro-inflammatory mediators (TNF-alpha, IL-1beta, NO) in serum and liver homogenates of thermally injured mice were significantly reduced by CORM-2 administration. This was accompanied by a decrease in the expression of iNOS while an increase in the expression of HO-1 in the liver tissue. In parallel, the concentrations of TNF-alpha and NO in supernatants of LPS-stimulated Kupffer cells co-incubated with CORM-2 (10-100 micromol/L) were also markedly decreased. Histological examination demonstrated that CORM-2 could attenuate the leukocytes infiltration to the liver tissue.
CORM-released CO modulates liver inflammation and significantly protects liver injury in burn mice by inhibiting the expression of iNOS and NO production, down-regulating the expression of pro-inflammatory mediators (TNF-alpha, IL-1beta).
探讨一氧化碳释放分子[二氯二羰基钌（II）二聚体，CORM-2]释放的一氧化碳对热损伤实验动物模型肝脏炎症反应的减轻作用，并研究其相关潜在机制。
在三个独立实验中将36只小鼠分为三组。在每个实验中，假手术组（n = 4）的小鼠接受假热损伤，烧伤组（n = 4）的小鼠接受15%体表面积（TBSA）的全层热损伤，烧伤+CORM-2组（n = 4）的小鼠接受相同热损伤并立即静脉注射CORM-2（8 mg/kg）。肝组织切片用苏木精和伊红染色并在光学显微镜下检查。通过生化方法测量转氨酶（ALT和AST）和一氧化氮（NO）水平。评估血清和组织匀浆中肿瘤坏死因子-α（TNF-α）和白细胞介素（IL-1β）活性以及诱导型一氧化氮合酶（iNOS）和血红素加氧酶-1（HO-1）的蛋白表达。在体外实验中，在存在或不存在CORM-2（10 - 100 μmol/L）的情况下，用脂多糖（LPS，10 μg/mL）刺激库普弗细胞4小时。随后，评估TNF-α的表达水平和NO的产生。
给予CORM-2后，热损伤小鼠血清和肝脏匀浆中的促炎介质（TNF-α、IL-1β、NO）显著降低。这伴随着肝脏组织中iNOS表达的降低以及HO-1表达的增加。同时，与CORM-2（10 - 100 μmol/L）共同孵育的LPS刺激的库普弗细胞上清液中TNF-α和NO的浓度也明显降低。组织学检查表明，CORM-2可减轻白细胞向肝组织的浸润。
CORM释放的一氧化碳通过抑制iNOS的表达和NO的产生、下调促炎介质（TNF-α、IL-1β）的表达来调节肝脏炎症并显著保护烧伤小鼠的肝损伤。
