Huang Yan, Lu Yi, Zhang Lei, Yan Jia, Jiang Jue, Jiang Hong
Department of Anesthesiology, School of Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200011, China.
Int J Mol Sci. 2014 Mar 6;15(3):4049-59. doi: 10.3390/ijms15034049.
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.
最近的研究表明,右美托咪定通过降低血清炎症因子水平发挥抗炎作用,然而,其上游机制仍不清楚。转录因子NF-κB进入细胞核并促进其靶基因的转录,包括编码促炎细胞因子IL-6和TNF-α的基因。在本研究中,我们建立了一个模拟临床手术过程的大鼠模型,以研究神经周围给予右美托咪定的抗炎作用及其潜在机制。右美托咪定在mRNA和蛋白质水平上均降低了坐骨神经中IL-6和TNF-α的水平。右美托咪定还抑制了活化的NF-κB向细胞核的转位以及NF-κB的结合活性。抗炎作用被证实具有剂量依赖性。最后,吡咯烷二硫代氨基甲酸盐也降低了IL-6和TNF-α的水平以及NF-κB的活化。总之,右美托咪定抑制了活化的NF-κB的核转位和结合活性,从而减少了炎性细胞因子。