BACKGROUND Chemokine C-C motif ligand 2 (CCL2) is one of the most widely recognised proinflammatory chemokines in cognitive disorders. Currently, CCL2-targeting drugs are extremely limited. Thus, this study aimed to explore the neuroprotection afforded by naringin in CCL2-induced cognitive impairment in rats. METHODS Before the CCL2 intra-hippocampal injection, rats were treated with naringin for 3 consecutive days via intraperitoneal injection. Two days post-surgery, the Morris water maze (MWM) and novel object recognition (NORT) tests were performed to detect spatial learning and memory and object cognition, respectively. Nissl staining and dUTP nick-end labelling (TUNEL) staining were performed to assess histopathological changes in the hippocampus. Commercial kits were used to measure the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the content of malondialdehyde (MDA). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine the relative mRNA expression of interleukin 1β, (IL-1β), interleukin 6 (IL-6), glutamate/aspartate transporter (GLAST), glutamate transporter-1 (GLT-1), phosphate-activated glutaminase (PAG), cysteine aspartic acid-specific protease 8 (caspase-8), cysteine aspartic acid-specific protease 3 (caspase-3), cell lymphoma/leukaemia-2 (Bcl-2), and Bcl-2 associated X protein (Bax). RESULTS In the MWM, the average escape latency and average swimming distance were significantly reduced and the crossing times were increased in the naringin-treated groups, compared with the CCL2 group. The NORT results revealed that, compared with the CCL2 rats, the discrimination index in the naringin-treated rats increased significantly. Nissl and TUNEL staining revealed that naringin protected the structure and survival of the neurons in the CA1 zone of the hippocampus. In the naringin-treated groups, the SOD and GSH-Px activities were increased, whereas the MDA levels were decreased. Furthermore, in the naringin-treated groups, the relative mRNA expression of IL-1β and IL-6 was significantly decreased; GLAST and GLT-1 mRNA expression levels were increased, whereas PAG was decreased. In the naringin-treated groups, the relative mRNA expression levels of caspase-8, caspase-3, and Bax were decreased, whereas that of Bcl-2 was increased. CONCLUSION Collectively, these data indicated that naringin alleviated the CCL2-induced cognitive impairment. The underlying mechanisms could be associated with the inhibition of neuroinflammation, oxidative stress, apoptosis, and the regulation of glutamate metabolism.

中文翻译：

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柚皮苷通过减弱海马中的神经元凋亡，在 CCL2 诱导的认知障碍中提供神经保护。

背景趋化因子CC基序配体2(CCL2)是认知障碍中最广泛认可的促炎趋化因子之一。目前，CCL2 靶向药物极为有限。因此，本研究旨在探讨柚皮苷对 CCL2 诱导的大鼠认知障碍的神经保护作用。方法在CCL2海马内注射前，大鼠连续3天经腹腔注射柚皮苷。术后两天，进行莫里斯水迷宫 (MWM) 和新物体识别 (NORT) 测试，分别检测空间学习和记忆以及物体认知。进行尼氏染色和 dUTP 缺口末端标记 (TUNEL) 染色以评估海马的组织病理学变化。商业试剂盒用于测量超氧化物歧化酶 (SOD) 和谷胱甘肽过氧化物酶 (GSH-Px) 的活性以及丙二醛 (MDA) 的含量。进行定量实时聚合酶链反应 (qRT-PCR) 以检查白介素 1β (IL-1β)、白介素 6 (IL-6)、谷氨酸/天冬氨酸转运蛋白 (GLAST)、谷氨酸转运蛋白-1 的相对 mRNA 表达(GLT-1)、磷酸激活谷氨酰胺酶 (PAG)、半胱氨酸天冬氨酸特异性蛋白酶 8 (caspase-8)、半胱氨酸天冬氨酸特异性蛋白酶 3 (caspase-3)、细胞淋巴瘤/白血病-2 (Bcl-2) ) 和 Bcl-2 相关的 X 蛋白 (Bax)。结果在MWM中，与CCL2组相比，柚皮苷治疗组的平均逃逸潜伏期和平均游泳距离显着降低，穿越次数增加。NORT 结果显示，与CCL2大鼠相比，柚皮苷处理组大鼠的辨别指数显着增加。Nissl 和 TUNEL 染色显示柚皮苷保护海马 CA1 区神经元的结构和存活。在柚皮苷处理组中，SOD 和 GSH-Px 活性增加，而 MDA 水平降低。此外，柚皮苷处理组中IL-1β和IL-6的相对mRNA表达显着降低；GLAST 和 GLT-1 mRNA 表达水平增加，而 PAG 减少。在柚皮苷处理组中，caspase-8、caspase-3和Bax的相对mRNA表达水平降低，而Bcl-2的相对mRNA表达水平升高。结论 总的来说，这些数据表明柚皮苷减轻了 CCL2 诱导的认知障碍。