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[外源性一氧化碳释放分子II对严重烧伤小鼠肝脏炎症反应的抑制作用]

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

作者信息

Sun Bing-Wei, Chen Xi, Chen Zhao-Yong, Kazuhiro Katada, Gediminas Cepinskas

机构信息

Department of Burns and Plastic Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, PR China.

出版信息

Zhonghua Shao Shang Za Zhi. 2007 Jun;23(3):179-83.

PMID:18019055
Abstract

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 CORM-2 after the same manipulation as sham group), burn (with 15% TBSA full-thickness burns), burn + CORM-2 (with 8 mg/kg CORM-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 + CORM-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.

摘要

目的

探讨外源性一氧化碳释放分子II对严重烧伤小鼠肝脏炎症反应的抑制作用及其潜在机制。

方法

将45只雄性C57BL/6小鼠随机分为假伤组(用37℃温水模拟烧伤)、假伤 + CORM - 2组(在与假伤组相同操作后给予8mg/kg CORM - 2)、烧伤组(15%体表面积全层烧伤)、烧伤 + CORM - 2组(在与烧伤组相同操作后给予8mg/kg CORM - 2)、烧伤 + DMSO组(在与烧伤组相同处理后给予DMSO),每组9只。于烧伤后24小时测定血清谷丙转氨酶(ALT)和谷草转氨酶(AST)水平,同时检测并评估髓过氧化物酶(MPO)、核因子(NF)κB、细胞间黏附分子(ICAM - 1)、血管细胞黏附分子(VCAM - 1)水平以及血清刺激后多形核白细胞与肝窦内皮细胞(HSECs)的黏附情况。

结果

与假伤组和烧伤 + CORM - 2组相比,烧伤组的ALT和AST水平(398±34,122±22)、MPO和NF - κB活性、ICAM - 1和VCAM - 1蛋白水平明显升高(P < 0.05或P < 0.01)。此外,烧伤组血清刺激后PMN与HSEC的黏附增强,而烧伤 + CORM - 2组血清刺激后该黏附明显受到抑制(P < 0.05)。

结论

外源性CORM - 2具有抑制NF - κB活性的能力,降低肝脏ICAM - 1和VCAM - 1的表达,从而减轻严重烧伤后白细胞的滞留,改善肝脏炎症反应,提高肝功能。

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