Inhibition of MAP kinase/NF-kB mediated signaling and attenuation of lipopolysaccharide induced severe sepsis by cerium oxide nanoparticles.
Inhibition of MAP kinase/NF-kB mediated signaling and attenuation of lipopolysaccharide induced severe sepsis by cerium oxide nanoparticles.
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DOI：
10.1016/j.biomaterials.2015.04.025
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发表时间：
2015-08
期刊：
影响因子：
14
通讯作者：
Blough ER
中科院分区：
文献类型：
--
作者：
Selvaraj V;Nepal N;Rogers S;Manne ND;Arvapalli R;Rice KM;Asano S;Fankhanel E;Ma JJ;Shokuhfar T;Maheshwari M;Blough ER
脓毒症是一种与高死亡率相关的危及生命的疾病。现有的治疗方法未能提高脓毒症患者的存活率。本研究的目的是评价纳米氧化铈(CeO2 NPs)能否通过预防雄性SD大鼠的肝功能障碍来预防脂多糖(LPS)诱导的严重脓毒症死亡。给脓毒症大鼠静脉注射单剂量(0.5 mg/kg)CeO2 NPs可显著提高存活率，并能使体温、呼吸频率和血压恢复到基线水平。治疗诱导的动物存活率的增加与肝脏损伤的减少、血清细胞因子/趋化因子的减少以及炎症相关信号的减少有关。Kupffer细胞和巨噬细胞暴露于CeO2 NPs后，细胞因子(肿瘤坏死因子-α、IL-1β、IL-6、HMGB1)释放减少，细胞内ROS减少，一氧化氮合酶(INOS)、环氧合酶-2(COX-2)水平降低，活化B细胞核因子-kappa型轻链增强剂(NFkB)转录活性降低。这项研究的结果表明，CeO2纳米粒子可能是一种有用的脓毒症治疗剂。
Sepsis is a life threatening disease that is associated with high mortality. Existing treatments have failed to improve survivability in septic patients. The purpose of this present study is to evaluate whether cerium oxide nanoparticles (CeO2NPs) can prevent lipopolysaccharide (LPS) induced severe sepsis mortality by preventing hepatic dysfunction in male Sprague Dawley rats. Administration of a single dose (0.5 mg/kg) of CeO2NPs intravenously to septic rats significantly improved survival rates and functioned to restore body temperature, respiratory rate and blood pressure towards baseline. Treatment-induced increases in animal survivability were associated with decreased hepatic damage along with reductions in serum cytokines/chemokines, and diminished inflammatory related signaling. Kupffer cells and macrophage cells exposed to CeO2NPs exhibited decreases in LPS-induced cytokine release (TNF-α, IL-1β, IL-6, HMGB1) which were associated with diminished cellular ROS, reduced levels of nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and decreased nuclear factor-kappa light chain enhancer of activated B cells (NF-kB) transcriptional activity. The findings of this study indicate that CeO2NPs may be useful as a therapeutic agent for sepsis.