Chitosan oligosaccharides protect mice from LPS challenge by attenuation of inflammation and oxidative stress
Chitosan oligosaccharides protect mice from LPS challenge by attenuation of inflammation and oxidative stress
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DOI：
10.1016/j.intimp.2010.10.016
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发表时间：
2011-01-01
影响因子：
5.6
通讯作者：
Du, Yu-Guang
中科院分区：
文献类型：
--
作者：
Qiao, Ying;Bai, Xue-Fang;Du, Yu-Guang
脓毒症及其衍生综合征是重症监护病房发病率和死亡率的主要原因。近年来大量研究表明，脓毒症的发生发展与机体氧化还原失衡和促炎细胞因子的过度产生有关。在以前的研究中，我们报道了壳寡糖的体外抗氧化和抗炎作用。鉴于这些发现，我们应用LPS注射的脓毒症小鼠模型来研究壳寡糖是否对LPS诱导的脓毒症具有保护作用。我们发现用壳寡糖治疗不仅减轻了器官功能障碍，而且提高了LPS注射后的存活率。为了进一步了解它是如何工作的，我们检查了几种促炎标志物，包括器官中的中性粒细胞浸润和血清中的TNF-α和IL-1 β，并发现这些细胞因子通过壳寡糖治疗显着减少。除此之外，抗氧化剂，包括谷胱甘肽（GSH）和过氧化氢酶（CAT）的水平被耗尽，丙二醛（MDA）的水平增加，在LPS诱导的脓毒症，而壳寡糖平滑的氧化还原失衡。此外，我们还评估了c-Jun NH 2-末端激酶和p38丝裂原活化蛋白激酶信号激活的LPS刺激，并发现他们都衰减壳寡糖治疗。总的来说，我们的数据表明，壳寡糖可以保护小鼠免受LPS的攻击，凭借抗炎作用以及抗氧化特性，这可能为脓毒症患者提供有益的效果。(C)2010爱思唯尔有限公司版权所有。
Sepsis and its derivative syndromes are major causes of morbidity and mortality in the intensive care unit. Recently, lots of studies have shown that the progression of sepsis is attributed to redox imbalance and overproduction of proinflammatory cytokines. In previous studies, we have reported the anti-oxidative and anti-inflammatory effects of chitosan oligosaccharides in vitro. In the light of these findings, we applied the model of sepsis to mice by LPS injection to investigate whether chitosan oligosaccharides have a protective effect on LPS-induced sepsis. We found that treatment by chitosan oligosaccharides not only attenuated organ dysfunction but also improved survival rate after LPS injection. To further understand how it works, we examined several proinflammatory markers including neutrophil infiltration in organs and TNF-alpha and IL-1 beta in serum, and found that these cytokines were significantly reduced by chitosan oligosaccharide treatment. In addition to this, anti-oxidants including glutathione (GSH) and catalase (CAT) levels were depleted and malondialdehyde (MDA) levels were increased in LPS-induced sepsis, while chitosan oligosaccharides smoothed out the redox imbalance. Furthermore, we also assessed c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase signal activation by LPS-stimulation, and found both of them were attenuated by chitosan oligosaccharide treatment. Collectively, our data demonstrated that chitosan oligosaccharides can protect mice from the LPS challenge by virtue of anti-inflammatory effects as well as anti-oxidation properties, which might offer beneficial effects for patients with sepsis. (C) 2010 Elsevier B.V. All rights reserved.