Protective effects of erythropoietin in traumatic spinal cord injury by inducing the Nrf2 signaling pathway activation
Protective effects of erythropoietin in traumatic spinal cord injury by inducing the Nrf2 signaling pathway activation
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DOI：
10.1097/ta.0000000000000211
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发表时间：
2014-05-01
影响因子：
3.4
通讯作者：
Liang, Weibang
中科院分区：
文献类型：
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作者：
Jin, Wei;Ming, Xing;Liang, Weibang
背景：促红细胞生成素已被证明对创伤性脊髓损伤（SCI）具有神经保护作用，但其潜在机制仍不清楚。抗氧化转录因子核因子红细胞 2 相关因子 2 (Nrf2) 的信号通路已被证明在保护 SCI 引起的继发性脊髓损伤中发挥重要作用。本研究旨在探讨重组人促红细胞生成素（rhEPO）对大鼠SCI后Nrf2信号通路激活及继发性脊髓损伤的影响。方法：对成年雄性Sprague-Dawley大鼠进行T8-T9椎板切除并用无血管夹压迫。分析了三组：(1) 假手术组、(2) SCI 组和(3) SCI + rhEPO 组（每组 n = 16）。在SCI + rhEPO组中，在SCI后30分钟以5,000 IU/kg的剂量给予rhEPO。创伤后72小时提取脊髓样本。 结果：结果，我们发现rhEPO治疗显着上调了Nrf2信号通路相关药物的信使RNA表达和活性，包括Nrf2、NAD(P) H：醌氧化还原酶1(NQO1)和谷胱甘肽S-转移酶。 rhEPO 的给药还显着改善了继发性脊髓损伤，表现为运动缺陷、脊髓水肿和细胞凋亡的严重程度降低。结论：SCI 后 rhEPO 给药在受损脊髓中诱导 Nrf2 介导的细胞保护反应，这可能是 rhEPO 改善 SCI 后预后的机制。 （J Trauma Acute Care Surg. 2014；76：1228-1234。版权所有 (C) 2014，Lippincott Williams & Wilkins）
BACKGROUND: Erythropoietin has demonstrated neuroprotective effects against traumatic spinal cord injury (SCI), but the underlying mechanisms remain unclear. The signaling pathway of an antioxidant transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), has been shown to play an important role in protecting SCI-induced secondary spinal cord damage. This study was undertaken to explore the effect of recombinant human erythropoietin (rhEPO) on the activation of Nrf2 signaling pathway and secondary spinal cord damage in rats after SCI.METHODS: Adultmale Sprague-Dawley rats were subjected to laminectomy at T8-T9 and compression with avascular clip. Three groups were analyzed: (1) sham group, (2) SCI group, and (3) SCI + rhEPO group (n = 16 per group). In the SCI + rhEPO group, rhEPO was administered at a dose of 5,000 IU/kg at 30 minutes after SCI. Spinal cord samples were extracted at 72 hours after the trauma.RESULTS: As a result, we found that the treatment with rhEPO markedly up-regulated the messenger RNA expressions and activities of Nrf2 signaling pathway-related agents, including Nrf2, NAD(P) H: quinone oxidoreductase 1(NQO1), and glutathione S-transferase. The administration of rhEPO also significantly ameliorated the secondary spinal cord damage, as shown by a decreased severity of locomotion deficit, spinal cord edema, and apoptosis.CONCLUSION: Post-SCI rhEPO administration induces Nrf2-mediated cytoprotective response in the injured spinal cord, and this may be a mechanism whereby rhEPO improves the outcome following SCI. (J Trauma Acute Care Surg. 2014; 76: 1228-1234. Copyright (C) 2014 by Lippincott Williams & Wilkins)