Activation of the Nrf2/ARE signaling pathway by probucol contributes to inhibiting inflammation and neuronal apoptosis after spinal cord injury

作者：Zhou Zipeng; Liu Chang; Chen Shurui; Zhao Haosen; Zhou Kang; Wang Wei; Yuan Yajiang; Li Zhuo; Guo Yue; Shen Zhaoliang; Mei Xifan

来源：Oncotarget, 2017, 8(32): 52078-52093.

DOI：10.18632/oncotarget.19107

• inflammation
• spinal cord injury
• Nrf2/ARE
• apoptosis
• probucol

The nuclear erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway plays an essential role in the cellular antioxidant and antiinflammatory responses. Spinal cord injury (SCI) results in a massive release of inflammatory factors and free radicals, which seriously compromise nerve recovery and axon regeneration. In this study, we examined the efficacy of probucol on antiinflammatory responses and functional recovery after SCI by activating the Nrf2/ARE signaling pathway. We also investigated the mechanism by which inflammation is inhibited in this process. We found that treatment of injured rats with probucol significantly increased levels of Nrf2, heme oxygenase-1 (HO-1) and NAD(P) H: quinone oxidoreductase-1 (NQO1), while levels of inflammatory cytokines, interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were decreased. This was associated with a reduction in neural cell apoptosis and promotion of nerve function recovery. These results demonstrate that the neuroprotective effects of probucol after SCI are mediated by activation of the Nrf2/ARE signaling pathway. These findings indicate that the anti-inflammatory effects of probucol represent a viable treatment for improving functional recovery following SCI.

• 出版日期2017-8-8