Yu De-shui, Cao Yang, Mei Xi-fan, Wang Yan-feng, Fan Zhong-kai, Wang Yan-song, Lv Gang
Department of Orthopaedics, The First Affiliated Hospital, Liaoning Medical University, People Street No. 5-2, GuTa District, Jinzhou 121001, Liaoning Province, People's Republic of China.
Department of Orthopaedics, The First Affiliated Hospital, Liaoning Medical University, People Street No. 5-2, GuTa District, Jinzhou 121001, Liaoning Province, People's Republic of China.
J Neurol Sci. 2014 Nov 15;346(1-2):51-9. doi: 10.1016/j.jns.2014.07.056. Epub 2014 Aug 4.
Previous studies have shown that curcumin (Cur) can produce potent neuroprotective effects against damage due to spinal cord injury (SCI). However, whether Cur can preserve the function of the blood-spinal cord barrier (BSCB) is unclear. The present study was performed to investigate the mechanism underlying BSCB permeability changes, which were induced by treatment with Cur (75, 150, and 300 mg/kg, i.p.) after compressive SCI in rats. BSCB permeability was evaluated by Evans blue leakage. Motor recovery of rats with SCI was assessed using the Basso, Beattie, and Bresnahan scoring system every day until the 21st days post-injury. The protein levels of heme oxygenase-1 (HO-1), tight junction protein, and inflammatory factors were analyzed by western blots. The expression of the inflammatory factors tumor necrosis factor-α (TNF-α) and nuclear factor-kappaB (NF-κB) mRNA was determined with reverse transcription-polymerase chain reactions. Treatment with Cur (150 and 300 mg/kg) significantly reduced Evans blue leakage into the spinal cord tissue at 24h after SCI. Cur (150 mg/kg) significantly increased HO-1 protein expression. The levels of TNF-α and NF-κB mRNA and protein greatly increased at 24h after SCI, and this increase was significantly attenuated by Cur treatment. ZO-1 and occludin expression was upregulated by Cur (150 mg/kg) treatment after SCI, and this effect was blocked by the HO-1 inhibitor zinc protoporphyrin. Long-term effects of Cur on motor recovery after SCI were observed. Our results indicated that Cur can improve motor function after SCI, which could correlate with improvements in BSCB integrity.
先前的研究表明,姜黄素(Cur)对脊髓损伤(SCI)所致损伤可产生强大的神经保护作用。然而,Cur是否能维持血脊髓屏障(BSCB)的功能尚不清楚。本研究旨在探讨大鼠压缩性SCI后经Cur(75、150和300mg/kg,腹腔注射)处理诱导的BSCB通透性变化的潜在机制。通过伊文思蓝渗漏评估BSCB通透性。每天使用Basso、Beattie和Bresnahan评分系统评估SCI大鼠的运动恢复情况,直至损伤后第21天。通过蛋白质免疫印迹法分析血红素加氧酶-1(HO-1)、紧密连接蛋白和炎性因子的蛋白水平。采用逆转录-聚合酶链反应测定炎性因子肿瘤坏死因子-α(TNF-α)和核因子-κB(NF-κB)mRNA的表达。Cur(150和300mg/kg)处理可显著减少SCI后24小时伊文思蓝向脊髓组织的渗漏。Cur(150mg/kg)可显著增加HO-1蛋白表达。SCI后24小时TNF-α和NF-κB mRNA及蛋白水平大幅升高,Cur处理可显著减弱这种升高。Cur(150mg/kg)处理后可上调SCI大鼠ZO-1和闭合蛋白的表达,且这种作用可被HO-1抑制剂原卟啉锌阻断。观察到Cur对SCI后运动恢复的长期影响。我们的结果表明,Cur可改善SCI后的运动功能,这可能与BSCB完整性的改善有关。