柚皮苷对ccl2诱导的认知障碍具有神经保护作用,其机制是减轻海马神经元凋亡。

IF 4.7 2区 心理学 Q1 BEHAVIORAL SCIENCES Behavioral and Brain Functions Pub Date : 2020-02-27 DOI:10.1186/s12993-020-00166-6
Jiang-Yi Long, Jian-Min Chen, Yuan-Jun Liao, Yi-Jun Zhou, Bing-Yu Liang, Yan Zhou
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引用次数: 16

摘要

背景:趋化因子C-C基序配体2 (CCL2)是认知障碍中最广泛认识的促炎趋化因子之一。目前,针对ccl2的药物非常有限。因此,本研究旨在探讨柚皮苷对ccl2诱导的大鼠认知功能障碍的神经保护作用。方法:大鼠在CCL2海马内注射前,连续3 d腹腔注射柚皮苷。术后2 d进行Morris水迷宫(MWM)和新物体识别(NORT)测试,分别检测空间学习记忆和物体认知。采用尼氏染色和dUTP镍端标记(TUNEL)染色评估海马组织病理变化。采用商品化试剂盒检测超氧化物歧化酶(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1β (IL-1β)、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X蛋白(Bax) mRNA的相对表达。结果:在MWM中,与CCL2组相比,柚皮苷处理组的平均逃避潜伏期和平均游泳距离明显缩短,穿越次数明显增加。NORT结果显示,与CCL2大鼠相比,柚皮素处理大鼠的识别指数明显升高。Nissl和TUNEL染色显示柚皮苷对海马CA1区神经元的结构和存活有保护作用。柚皮素处理组SOD和GSH-Px活性升高,MDA水平降低。柚皮素处理组IL-1β、IL-6 mRNA相对表达量显著降低;GLAST和GLT-1 mRNA表达水平升高,PAG表达水平降低。柚皮素处理组caspase-8、caspase-3、Bax mRNA相对表达量降低,Bcl-2 mRNA相对表达量升高。结论:综上所述,这些数据表明柚皮苷减轻了ccl2诱导的认知功能障碍。其潜在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。
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Naringin provides neuroprotection in CCL2-induced cognition impairment by attenuating neuronal apoptosis in the hippocampus.

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.

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来源期刊
Behavioral and Brain Functions
Behavioral and Brain Functions 医学-行为科学
CiteScore
5.90
自引率
0.00%
发文量
11
审稿时长
6-12 weeks
期刊介绍: A well-established journal in the field of behavioral and cognitive neuroscience, Behavioral and Brain Functions welcomes manuscripts which provide insight into the neurobiological mechanisms underlying behavior and brain function, or dysfunction. The journal gives priority to manuscripts that combine both neurobiology and behavior in a non-clinical manner.
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