Dexmedetomidine inhibits the secretion of high mobility group box 1 from lipopolysaccharide-activated macrophages In vitro

被引:61
作者
Chang, Yulin [1 ]
Huang, Xiaojing [2 ]
Liu, Zhaohui [1 ]
Han, Guangwei [3 ]
Huang, Lina [3 ]
Xiong, Yuan-Chang [2 ]
Wang, Zhengping [4 ]
机构
[1] Hebei Med Univ, Cangzhou Cent Hosp, Dept Anesthesiol, Shijiazhuang, Hebei, Peoples R China
[2] Second Mil Univ, Changhai Hosp, Dept Anesthesiol, Shanghai, Peoples R China
[3] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1, Dept Anesthesiol, Shanghai 200030, Peoples R China
[4] Tongji Univ, Shanghai Peoples Hosp 10, Dept Anesthesiol, Sch Med, Shanghai 200072, Peoples R China
关键词
Dexmedetomidine; High mobility group box 1; Lipopolysaccharides; NF-kappa B; alpha 2-Adrenergic receptors; ISCHEMIA-REPERFUSION INJURY; LUNG INJURY; ENDOTOXIN; RATS; HMGB1; SHOCK; CYTOKINE; RECEPTOR; MICE; PATHOGENESIS;
D O I
10.1016/j.jss.2012.07.017
中图分类号
R61 [外科手术学];
学科分类号
100210 [外科学];
摘要
Background: High mobility group box 1 (HMGB1) is a critical proinflammatory factor that is closely related to mortality in sepsis patients. Dexmedetomidine has been proven to reduce the mortality rate from endotoxin shock and attenuate endotoxin-induced acute lung injury. These effects result from reduced secretion of many proinflammatory mediators, although it is not clear whether dexmedetomidine affects the secretion of HMGB1. In this study, we explored the effect of dexmedetomidine on the expression and secretion of HMGB1 from lipopolysaccharide (LPS)-activated macrophages. Methods: We incubated RAW264.7 cells with LPS in the presence or absence of various concentrations of dexmedetomidine. We used an enzyme-linked immunosorbent assay to detect the secretion levels of HMGB1 in the culture supernatant. We employed real-time polymerase chain reaction to assess the expression of HMGB1 mRNA, and used a nuclear/cytoplasm extraction kit to extract the nuclear and cytoplasmic proteins. We employed Western blotting to observe changes in the translocation of HMGB1 from the nucleus to the cytoplasm. In addition, we used a nuclear factor (NF)-kappa B p50/p65 transcription factor assay kit to analyze NF-kappa B activity in the nuclear extract. Results: Dexmedetomidine inhibited the translocation of HMGB1 from the nucleus to the cytoplasm and its extracellular secretion in LPS-activated macrophages while suppressing the expression of HMGB1 mRNA. Dexmedetomidine inhibited the translocation of NF-kappa B from the cytoplasm to the nucleus in LPS-activated macrophages in a dose-dependent manner. Moreover, these effects were significantly reversed by the alpha 2-adrenergic receptor antagonist yohimbine. Conclusions: Our study demonstrates that dexmedetomidine inhibits the translocation of HMGB1 from the nucleus to the cytoplasm and the expression of HMGB1 mRNA at clinically relevant dosages. The mechanism responsible for these effects may be through the NF-kappa B signaling pathway and the alpha 2-adrenergic receptors. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved.
引用
收藏
页码:308 / 314
页数:7
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