Firat Tulin, Kukner Aysel, Ayturk Nilufer, Gezici Ali Rıza, Serin Erdinc, Ozogul Candan, Tore Fatma
Department of Histology and Embryology, Faculty of Medicine, Abant Izzet Baysal University, Bolu, Turkey. Email:
Department of Histology and Embryology, Faculty of Medicine, Near East University, Nicosia, Cyprus.
Cell J. 2021 Nov;23(6):701-707. doi: 10.22074/cellj.2021.7198. Epub 2021 Nov 23.
In spinal cord injury (SCI), the primary mechanical damage leads to a neuroinflammatory response and the secondary neuronal injury occurs in response to the release of reactive oxygen species (ROS). In addition to the suppression of inflammation, autophagy plays a significant role in the survival of neurons during secondary SCI. The present study aimed to examine the anti-inflammatory and autophagic effects of agmatine and rapamycin in SCI and to compare the results with methylprednisolone (MP) used in the clinic.
In this animal-based experimental study, thirty adult male Sprague-Dawley rats were randomly divided into five groups as sham-control, injury, injury+MP, injury+rapamycin, injury+agmatine groups. SCI was induced by compressing the T7-8-9 segments of the spinal cord, using an aneurysm clip for one minute, and then rats were treated daily for 7 days. Seven days post-treatment, damaged spinal cord tissues of sacrificed rats were collected for microscopic and biochemical examinations using histopathologic and transmission electron microscope (TEM) scores. Malondialdehyde (MDA) and glutathione peroxidase (GPx) levels were spectrophotometrically measured.
The results of this study showed that the damaged area was smaller in the rapamycin group when compared to the MP group. Many autophagic vacuoles and macrophages were observed in the rapamycin group. Degeneration of axon, myelin, and wide edema was observed in SCI by electron microscopic observations. Fragmented myelin lamellae and contracted axons were also noted. While MDA and GPx levels were increased in the injury group, MDA levels were significantly decreased in the agmatine and MP groups, and GPx levels were decreased in the rapamycin group.
The results of our study confirmed that rapamycin and agmatine can be an effective treatment for secondary injury of SCI.
在脊髓损伤（SCI）中，原发性机械损伤会引发神经炎症反应，而继发性神经元损伤则是由活性氧（ROS）释放所导致。除了抑制炎症外，自噬在继发性脊髓损伤期间神经元的存活中也起着重要作用。本研究旨在探讨胍丁胺和雷帕霉素在脊髓损伤中的抗炎和自噬作用，并将结果与临床上使用的甲基强的松龙（MP）进行比较。
在这项基于动物的实验研究中，30只成年雄性Sprague-Dawley大鼠被随机分为五组，即假手术对照组、损伤组、损伤+MP组、损伤+雷帕霉素组、损伤+胍丁胺组。使用动脉瘤夹压迫脊髓T7-8-9节段一分钟诱导脊髓损伤，然后大鼠每天接受治疗，持续7天。治疗7天后，处死大鼠，收集受损脊髓组织，采用组织病理学和透射电子显微镜（TEM）评分进行微观和生化检查。通过分光光度法测量丙二醛（MDA）和谷胱甘肽过氧化物酶（GPx）水平。
本研究结果表明，与MP组相比，雷帕霉素组的损伤面积更小。在雷帕霉素组中观察到许多自噬空泡和巨噬细胞。通过电子显微镜观察发现脊髓损伤中存在轴突、髓鞘变性和广泛水肿。还注意到髓鞘板层断裂和轴突收缩。损伤组中MDA和GPx水平升高，而胍丁胺组和MP组中MDA水平显著降低，雷帕霉素组中GPx水平降低。
我们的研究结果证实，雷帕霉素和胍丁胺可有效治疗脊髓损伤的继发性损伤。
