title: Perineural dexmedetomidine attenuates inflammation in rat sciatic nerve via the NF-κB pathway.
abstract: Recent studies have shown that dexmedetomidine exerts an anti-inflammatory effect by reducing serum levels of inflammatory factors, however, the up-stream mechanism is still unknown. The transcription factor NF-κB enters the nucleus and promotes the transcription of its target genes, including those encoding the pro-inflammatory cytokines IL-6 and TNF-α. In this study, we established a rat model that simulates a clinical surgical procedure to investigate the anti-inflammatory effect of perineural administration of dexmedetomidine and the underlying mechanism. Dexmedetomidine reduced the sciatic nerve levels of IL-6 and TNF-α at both the mRNA and protein level. Dexmedetomidine also inhibited the translocation of activated NF-κB to the nucleus and the binding activity of NF-κB. The anti-inflammatory effect is confirmed to be dose-dependent. Finally, pyrrolidine dithiocarbamate also reduced the levels of IL-6 and TNF-α and the activation of NF-κB. In conclusion, dexmedetomidine inhibited the nuclear translocation and binding activity of activated NF-κB, thus reducing inflammatory cytokines.
authors.affiliation: Department of Anesthesiology, School of Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200011, China. huangyan606@126.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, School of Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200011, China. luyi077@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, School of Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200011, China. weiymzhl@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, School of Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200011, China. mzkyanj@163.com.
authors.forename: Jia
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Anesthesiology, School of Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200011, China. jiangjue1136@sina.com.
authors.forename: Jue
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology, School of Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200011, China. dr_jianghong@163.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D015153:Blotting, Western; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D020927:Dexmedetomidine