Naringin provides neuroprotection in CCL2-induced cognition impairment by attenuating neuronal apoptosis in the hippocampus
Naringin provides neuroprotection in CCL2-induced cognition impairment by attenuating neuronal apoptosis in the hippocampus
复制标题
柚皮苷通过减弱海马神经元凋亡来为 CCL2 诱导的认知障碍提供神经保护。
DOI：
10.1186/s12993-020-00166-6
复制
发表时间：
2020-02-27
影响因子：
5.1
通讯作者：
Zhou, Yan
中科院分区：
文献类型：
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作者：
Long, Jiang-yi;Chen, Jian-min;Zhou, Yan
背景趋化因子C-C基序配体2（CCL 2）是认知障碍中最广泛认可的促炎性趋化因子之一。目前，针对CCL 2的药物非常有限。因此，本研究旨在探讨柚皮苷对CCL 2诱导的大鼠认知障碍的神经保护作用。方法在海马注射CCL 2前，连续3 d腹腔注射柚皮苷。术后第2天，分别进行Morris水迷宫（MWM）和新物体识别（NORT）测试，以检测空间学习记忆和物体认知。尼氏染色和dUTP缺口末端标记（TUNEL）染色进行评估海马组织病理学变化。用商品化试剂盒测定超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）活性及丙二醛（MDA）含量。采用实时定量聚合酶链反应（qRT-PCR）检测白细胞介素1 β的相对mRNA表达，（IL-1 β）、白细胞介素6（IL-6）、谷氨酸/天冬氨酸转运蛋白（GLAST）、谷氨酸转运蛋白-1（GLT-1）、磷酸活化的丙氨酸氨基转移酶（PAG）、半胱氨酸天冬氨酸特异性蛋白酶8（半胱天冬酶-8）、半胱氨酸天冬氨酸特异性蛋白酶3（半胱天冬酶-3）、细胞淋巴瘤/白血病-2（Bcl-2）和Bcl-2相关X蛋白（Bax）。结果在MWM中，与CCL 2组相比，柚苷处理组的平均逃避潜伏期和平均游泳距离明显缩短，穿越次数增加。NORT结果显示，与CCL 2大鼠相比，柚皮苷处理的大鼠的辨别指数显著增加。Nissl和TUNEL染色显示，柚皮苷保护海马CA 1区神经元的结构和存活。柚苷处理组SOD、GSH-Px活性升高，MDA含量降低。此外，在柚苷处理组中，IL-1 β和IL-6的相对mRNA表达显著降低; GLAST和GLT-1 mRNA表达水平升高，而PAG降低。柚皮苷处理组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。结论柚皮苷可减轻CCL 2所致的认知功能损害。其机制可能与抑制神经炎症、氧化应激、细胞凋亡和调节谷氨酸代谢有关。
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 1 beta, (IL-1 beta), 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-1 beta 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.