二氢杨梅素通过抑制大鼠NLRP3减轻癫痫和认知障碍。

Dihydromyricetin mitigates epilepsy and cognitive impairment via NLRP3 inhibition in rats.

作者信息

Li Qing, Qu Zhenzhen, Mao Zhuofeng, Jia Lijing, Qiao Qi, Zhang Yange, Zhou Kaiping, Che Liqin, Wang Weiping

机构信息

Department of Neurology, Key Laboratory of Neurology of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China.

出版信息

Folia Neuropathol. 2025;63(1):51-66. doi: 10.5114/fn.2025.149520.

DOI:10.5114/fn.2025.149520

PMID:40353378

Abstract

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.

摘要

引言

含核苷酸结合结构域富含亮氨酸重复序列的家族含吡啉结构域3（NLRP3）炎性小体通过其在炎症和细胞焦亡中的作用，与包括癫痫在内的多种神经系统疾病有关。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对癫痫中NLRP3炎性小体途径及相关认知障碍的影响尚未完全明确。在此，我们评估了DHM是否能通过调节NLRP3炎性小体减轻毛果芸香碱诱导的大鼠海马体神经元损伤及学习和记忆障碍。

材料与方法

建立癫痫大鼠模型，记录自发复发性癫痫（SRS）的频率和持续时间。采用尼氏染色评估海马锥体细胞的功能。利用蛋白质免疫印迹法、实时逆转录聚合酶链反应和酶联免疫吸附测定法检测海马中NLRP3炎症途径相关因子的变化。通过莫里斯水迷宫试验、海马晚期长时程增强记录及相关突触蛋白表达评估来验证认知功能。

结果

癫痫持续状态（SE）诱导后用DHM治疗可降低接受毛果芸香碱的大鼠的SRS频率和时长，表明DHM有改善大鼠SE诱导后的长时程增强和认知缺陷的潜力。此外，在大鼠诱导SE后，DHM可提高突触蛋白的表达。它可能预防海马锥体细胞受到损伤，且DHM诱导的神经保护作用可能与癫痫大鼠中与NLRP3相关的细胞焦亡有关。DHM可防止海马锥体细胞受到损伤。