Wang Rui-Ke, Zhang Qin-Qin, Pan Yun-Dan, Guo Qu-Lian
Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Exp Ther Med. 2013 Feb;5(2):581-585. doi: 10.3892/etm.2012.810. Epub 2012 Nov 13.
In the present study, we examined the effect of etanercept on high mobility group box 1 (HMGB1) expression in dorsal root ganglion (DRG) neuron cells in a rat model of chronic constriction injury (CCI) of the sciatic nerve, with the aim of exploring the molecular mechanism underlying the therapeutic effect of etanercept on sciatica-related nociception and the potential interaction between tumor necrosis factor-α (TNF-α) and HMGB1 in DRG neuron cells. A rat CCI model was employed and the animals were randomly assigned to seven groups (n=20/group): untreated, sham only, sham/saline, sham/etanercept, CCI only, CCI/saline and CCI/etanercept. Our results revealed that compared with the sham/saline and sham/etanercept groups, thermal hyperalgesia and mechanical hyperalgesia, as well as HMGB1 expression at both the mRNA and protein levels in the DRG neuron cells, were induced by CCI, and were significantly inhibited by etanercept. Although etanercept showed no significant effect on the sham group, it significantly reduced the phosphorylated p38 mitogen-activated protein kinase (MAPK) levels induced by CCI in the DRG neuron cells. In conclusion, we demonstrated that etanercept significantly decreased the HMGB1 expression induced by CCI in the DRG neuron cells. This study not only explored the molecular mechanisms underlying the therapeutic effect of etanercept on sciatica-related nociception, but also provided indirect evidence for an interaction between TNF-α and HMGB1 in DRG neuron cells.
在本研究中，我们在坐骨神经慢性压迫损伤（CCI）大鼠模型中，研究了依那西普对背根神经节（DRG）神经元细胞中高迁移率族蛋白B1（HMGB1）表达的影响，旨在探索依那西普对坐骨神经痛相关伤害感受治疗作用的分子机制，以及肿瘤坏死因子-α（TNF-α）与DRG神经元细胞中HMGB1之间的潜在相互作用。采用大鼠CCI模型，将动物随机分为七组（每组n = 20）：未治疗组、仅假手术组、假手术/生理盐水组、假手术/依那西普组、仅CCI组、CCI/生理盐水组和CCI/依那西普组。我们的结果显示，与假手术/生理盐水组和假手术/依那西普组相比，CCI诱导了热痛觉过敏和机械性痛觉过敏，以及DRG神经元细胞中HMGB1在mRNA和蛋白水平的表达，而依那西普显著抑制了这些表达。虽然依那西普对假手术组无显著影响，但它显著降低了CCI诱导的DRG神经元细胞中磷酸化p38丝裂原活化蛋白激酶（MAPK）水平。总之，我们证明依那西普显著降低了CCI诱导的DRG神经元细胞中HMGB1的表达。本研究不仅探索了依那西普对坐骨神经痛相关伤害感受治疗作用的分子机制，还为TNF-α与DRG神经元细胞中HMGB1之间的相互作用提供了间接证据。
