Oruk Sezai, Ergul Erkec Ozlem, Huyut Zubeyir, Acikgoz Eda
Department of Medical Physiology, Institute of Health Sciences, Van Yuzuncu Yil University, Van, Turkey.
Department of Physiology, Faculty of Medicine, Van Yuzuncu Yil University, Van, Turkey.
Metab Brain Dis. 2025 Apr 11;40(4):176. doi: 10.1007/s11011-025-01603-z.
Multiple sclerosis (MS) is an inflammatory central nervous system disease characterized by demyelination and axonal loss and is the main cause of non-traumatic neurological disability in young adults. Although there are several treatment approaches to manage the disease, there is no definitive cure for multiple sclerosis. Inflammation and oxidative stress are known to play important roles in the pathophysiology of MS. Ghrelin, a peptide secreted by the stomach, is reported to have neuroprotective properties through several pathways, including attenuating oxidative stress and inflammation. In the present study cuprizone (CPZ)-induced model of MS was used in Wistar albino rats to study the possible anti-inflammatory, antioxidant and neuroprotective effects of ghrelin. Rats were randomly divided into six groups: Control groups (Control and Control-S), demyelination group, remyelination group, remyelination + ghrelin (20 µg/kg) group and remyelination + ghrelin (40 µg/kg) group. Y maze test was performed on the rats on their last day of the experiment. Oxidative stress and inflammatory parameters were investigated in brain using commercial kits by enzyme-linked immunosorbent assay (ELISA). Luxol fast blue (LFB) and hematoxylen&eosin (H&E) staining were performed in brain tissues. CPZ leads to a significant decrease in glutathione peroxidase (GSH-Px) levels and myelin content and a significant increase in malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-ɑ), interleukin- 6 (IL- 6) levels, the number of lymphatic cells and inflammatory cells. A significant increase in the antioxidant parameter levels and a significant decrease in MDA levels were found in the ghrelin treated groups (p < 0.05). CPZ leads to irregular, fragmented, demyelinating nerve fibers. A more significant remyelination was observed in the ghrelin treated groups compared to the other groups (p < 0.05). In conclusion, ghrelin treatment showed neuroprotective and antioxidant properties and reduced demyelination in the CPZ-induced rat model of multiple sclerosis.
多发性硬化症（MS）是一种以脱髓鞘和轴突丢失为特征的炎症性中枢神经系统疾病，是年轻成年人非创伤性神经残疾的主要原因。尽管有几种治疗方法来管理这种疾病，但多发性硬化症尚无确切的治愈方法。已知炎症和氧化应激在MS的病理生理学中起重要作用。胃泌素是一种由胃分泌的肽，据报道通过多种途径具有神经保护特性，包括减轻氧化应激和炎症。在本研究中，使用Wistar白化大鼠的 cuprizone（CPZ）诱导的MS模型来研究胃泌素可能的抗炎、抗氧化和神经保护作用。大鼠被随机分为六组：对照组（对照和对照-S）、脱髓鞘组、再髓鞘化组、再髓鞘化+胃泌素（20μg/kg）组和再髓鞘化+胃泌素（40μg/kg）组。在实验的最后一天对大鼠进行Y迷宫测试。使用商业试剂盒通过酶联免疫吸附测定（ELISA）在脑中研究氧化应激和炎症参数。在脑组织中进行Luxol固蓝（LFB）和苏木精&伊红（H&E）染色。CPZ导致谷胱甘肽过氧化物酶（GSH-Px）水平和髓磷脂含量显著降低，丙二醛（MDA）、肿瘤坏死因子-α（TNF-ɑ）、白细胞介素-6（IL-6）水平、淋巴细胞和炎症细胞数量显著增加。在胃泌素治疗组中发现抗氧化参数水平显著增加，MDA水平显著降低（p<0.05）。CPZ导致神经纤维不规则、碎片化、脱髓鞘。与其他组相比，在胃泌素治疗组中观察到更显著的再髓鞘化（p<0.05）。总之，胃泌素治疗在CPZ诱导的大鼠多发性硬化症模型中显示出神经保护和抗氧化特性，并减少了脱髓鞘。
