Fakhri Sajad, Sabouri Shahryar, Kiani Amir, Farzaei Mohammad Hosein, Rashidi Khodabakhsh, Mohammadi-Farani Ahmad, Mohammadi-Noori Ehsan, Abbaszadeh Fatemeh
Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Korean J Pain. 2022 Jul 1;35(3):291-302. doi: 10.3344/kjp.2022.35.3.291.
Spinal cord injury (SCI) is one of the most debilitating disorders throughout the world, causing persistent sensory-motor dysfunction, with no effective treatment. Oxidative stress and inflammatory responses play key roles in the secondary phase of SCI. Naringenin (NAR) is a natural flavonoid with known anti-inflammatory and antioxidative properties. This study aims at evaluating the effects of intrathecal NAR administration on sensory-motor disability after SCI.
Animals underwent a severe compression injury using an aneurysm clip. About 30 minutes after surgery, NAR was injected intrathecally at the doses of 5, 10, and 15 mM in 20 μL volumes. For the assessment of neuropathic pain and locomotor function, acetone drop, hot plate, inclined plane, and Basso, Beattie, Bresnahan tests were carried out weekly till day 28 post-SCI. Effects of NAR on matrix metalloproteinase (MMP)-2 and MMP-9 activity was appraised by gelatin zymography. Also, histopathological analyses and serum levels of glutathione (GSH), catalase and nitrite were measured in different groups.
NAR reduced neuropathic pain, improved locomotor function, and also attenuated SCI-induced weight loss weekly till day 28 post-SCI. Zymography analysis showed that NAR suppressed MMP-9 activity, whereas it increased that of MMP-2, indicating its anti-neuroinflammatory effects. Also, intrathecal NAR modified oxidative stress related markers GSH, catalase, and nitrite levels. Besides, the neuroprotective effect of NAR was corroborated through increased survival of sensory and motor neurons after SCI.
These results suggest intrathecal NAR as a promising candidate for medical therapeutics for SCI-induced sensory and motor dysfunction.
脊髓损伤（SCI）是全球最使人衰弱的疾病之一，会导致持续的感觉运动功能障碍，且尚无有效治疗方法。氧化应激和炎症反应在SCI的继发阶段起关键作用。柚皮素（NAR）是一种具有抗炎和抗氧化特性的天然黄酮类化合物。本研究旨在评估鞘内注射NAR对SCI后感觉运动功能障碍的影响。
使用动脉瘤夹对动物造成严重压迫性损伤。术后约30分钟，以5、10和15 mM的剂量将NAR以20 μL的体积鞘内注射。为评估神经病理性疼痛和运动功能，每周进行丙酮滴注、热板、斜面以及Basso、Beattie、Bresnahan测试，直至SCI后第28天。通过明胶酶谱法评估NAR对基质金属蛋白酶（MMP）-2和MMP-9活性的影响。此外，还对不同组进行了组织病理学分析以及谷胱甘肽（GSH）、过氧化氢酶和亚硝酸盐的血清水平测定。
NAR减轻了神经病理性疼痛，改善了运动功能，并且在SCI后第28天之前每周都减轻了SCI引起的体重减轻。酶谱分析表明，NAR抑制了MMP-9的活性，而增加了MMP-2的活性，表明其具有抗神经炎症作用。此外，鞘内注射NAR改变了氧化应激相关标志物GSH、过氧化氢酶和亚硝酸盐的水平。此外，SCI后感觉和运动神经元存活率的提高证实了NAR的神经保护作用。
这些结果表明鞘内注射NAR有望成为治疗SCI引起的感觉和运动功能障碍的医学疗法。
