二氢杨梅素通过抑制NLRP3减轻大鼠癫痫和认知障碍。

IF 1.5 4区 医学 Q4 NEUROSCIENCES
Qing Li, Zhenzhen Qu, Zhuofeng Mao, Lijing Jia, Qi Qiao, Yange Zhang, Kaiping Zhou, Liqin Che, Weiping Wang
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引用次数: 0

摘要

简介:富含亮氨酸重复序列的核苷酸结合结构域家族pyrin结构域- 3 (NLRP3)炎性小体通过其在炎症和焦亡中的作用与许多神经系统疾病(包括癫痫)有关。二氢杨梅素(DHM)对神经系统疾病患者具有神经保护作用。然而,DHM对癫痫及相关认知障碍中NLRP3炎性体通路的影响尚不完全清楚。本研究评估DHM是否能通过调节NLRP3炎性体减轻匹罗卡品诱导的大鼠海马体神经元损伤和学习记忆障碍。材料与方法:建立癫痫大鼠模型,记录自发性再发作(SRS)频率和持续时间。采用尼氏染色评价海马锥体神经元的功能。采用Western blotting、实时逆转录聚合酶链反应和酶联免疫吸附法检测海马NLRP3炎症通路相关因子的变化。采用Morris水迷宫实验、海马后期长时程增强记录和相关突触蛋白表达评估验证认知功能。结果:在癫痫持续状态(SE)诱导后用DHM治疗可减少服用匹罗卡平的大鼠SRS的频率和长度,提示DHM有可能改善大鼠SE诱导后的长期增强和认知缺陷。DHM诱导大鼠SE后,使突触蛋白表达升高。它可以预防海马锥体神经元的损伤,dhm诱导的神经保护可能与癫痫大鼠NLRP3相关的焦亡有关。DHM对海马锥体神经元有保护作用。结论:我们发现DHM通过抑制焦亡和炎症对癫痫及其合并症的认知功能障碍有治疗作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dihydromyricetin mitigates epilepsy and cognitive impairment via NLRP3 inhibition in rats.

Introduction: The nucleotide-binding domain leucine-rich repeat-containing family pyrin domain-containing 3 (NLRP3) inflammasome has been implicated in numerous neurological disorders, including epilepsy, through its role in inflammation and pyroptosis. Dihydromyricetin (DHM) has neuroprotective effects in patients with neurological disorders. However, the impact of DHM on the NLRP3 inflammasome pathway in epilepsy and related cognitive impairment is yet to be fully understood. Herein, we evaluated whether DHM can alleviate pilocarpine-induced neuronal injury and learning and memory disorders in the hippocampal body of rats by regulating the NLRP3 inflammasome.

Material and methods: An epileptic rat model was established, and spontaneous recurrent seizure (SRS) frequency and duration were recorded. The function of hippocampal pyramidal neurons was evaluated using Nissl staining. Western blotting, real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays were used to detect changes in NLRP3 inflammatory pathway-related factors in the hippocampus. Cognitive function was verified using the Morris water maze test, hippocampal late-phase long-term potentiation recording and associated synaptic protein expression assessment.

Results: Treatment with DHM after status epilepticus (SE) induction decreases the frequency and length of SRS in rats receiving pilocarpine, suggesting that DHM has the potential to improve long-term potentiation and cognitive deficits after SE induction in rats. Additionally, after inducing SE in rats, DHM raises the expression of synaptic proteins. It may prevent harm to hippocampal pyramidal neurons, and DHM-induced neuroprotection may contribute to the pyroptosis associated with NLRP3 in epileptic rats. DHM guards against harm to hippocampus pyramidal neurons.

Conclusions: We found that DHM plays a role in treating epilepsy and its comorbid cognitive impairment by inhibiting pyroptosis and inflammation.

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来源期刊
Folia neuropathologica
Folia neuropathologica 医学-病理学
CiteScore
2.50
自引率
5.00%
发文量
38
审稿时长
>12 weeks
期刊介绍: Folia Neuropathologica is an official journal of the Mossakowski Medical Research Centre Polish Academy of Sciences and the Polish Association of Neuropathologists. The journal publishes original articles and reviews that deal with all aspects of clinical and experimental neuropathology and related fields of neuroscience research. The scope of journal includes surgical and experimental pathomorphology, ultrastructure, immunohistochemistry, biochemistry and molecular biology of the nervous tissue. Papers on surgical neuropathology and neuroimaging are also welcome. The reports in other fields relevant to the understanding of human neuropathology might be considered.
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