外源性一氧化碳释放分子对脓毒症小鼠神经系统抗炎的调节作用

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摘要目的: 探讨外源性一氧化碳释放分子（carbon monoxide-releasing molecule-2，CORM-2）干预在脓毒症小鼠神经系统抗炎中的调节作用及其可能的机制。方法: 采用盲肠结扎穿孔（cecal ligation and puncture，CLP）法建立脓毒症模型。48只雄性昆明种小鼠，随机分为假手术组、CLP模型组、CORM-2干预组和卡巴胆碱组。CLP术后24 h处死小鼠并收集血浆、脑组织标本。分别检测脑组织中TNF-α、IL-6等炎症因子的表达，神经抗炎递质乙酰胆碱的表达以及血清乙酰胆碱酯酶活性。测定脑组织湿/干重比并观察脑组织病理变化。结果: 与CLP模型组比较，CORM-2干预组和卡巴胆碱组脑间质水肿程度减轻，白细胞浸润明显减少;脑组织中细胞因子的表达水平明显下调（P < 0.05）;脑内神经抗炎递质乙酰胆碱浓度较CLP组增加（P <0.05），血清乙酰胆碱酯酶的活性较CLP组减弱（P <0.05）。结论: CORM-2干预脓毒症小鼠，能够下调细胞因子水平，增加神经抗炎递质的表达，在神经系统抗炎中起到一定的增强作用。

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	仇雪枫
	孙炳伟
	王敏
	孙艳
	杨国涛
	王波

关键词 ：脓毒症, 一氧化碳, 乙酰胆碱, 胆碱能抗炎通路

Abstract：Objective: To investigate the regulation effects of exogenous carbon monoxide-releasing molecule-2（CORM-2）on the nervous system in septic mice. Methods: To make standard cecal ligation and puncture（CLP）models，48 C57BL/6 mice were randomly divided into 4 groups: sham group，CLP group，CORM-2 intervention group and Carbachol group. The animals were sacrificed at 24 hours after experimental manipulation. Serum and brain tissue samples were collected，the expression of TNF-α，IL-6，neural expression of anti-inflammatory neurotransmitter acetylcholine（ACh），and the acetylcholinesterase（AChE）activity of brain tissues. To measure the wet-to-dry weight ratio of brain tissues and the pathology changes of brain tissues were also observed by HE dyeing. Results: Compared with the CLP mice，tissues injuries，pro-inflammatory cytokines（TNF-α and IL-6）expressions were markedly down regulated in CORM-2 and Carbachol intervention groups; while the concentration of neurotransmitter ACh were increased，and the ac tivity of AChE were inhibited in CORM-2 and Carbachol intervention mice. Conclusion: Taken together，the data of this study showed that CORM-2 intervention markedly inhibited inflammatory responses in the nervous system，indicating that the CORM-2 may play an important roles in the treatment of sepsis，and will be useful for the clinical treatment of critically ill patients in the future.

Key words： sepsis carbon monoxide acetylcholine cholinergic antiinflammatory pathway

基金资助:

国家自然科学基金资助项目（30772256， 81071546）;江苏省自然科学基金资助项目（BK2008237）

通讯作者: 孙炳伟（通讯作者），教授，博士生导师，E-mail:sunbinwe@hotmail.com

作者简介: 仇雪枫（1979—），男，硕士研究生

引用本文:

仇雪枫，孙炳伟，王敏，孙艳，杨国涛，王波. 外源性一氧化碳释放分子对脓毒症小鼠神经系统抗炎的调节作用[J]. 江苏大学学报:医学版, 2012, 22(2): 110-113.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2012/V22/I2/110

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