The neuroprotective effect of Dl-3-n-butylphthalide in epileptic rats via inhibiting endoplasmic reticulum stress.

IF 1.5 4区医学 Q4 NEUROSCIENCES

Folia neuropathologica Pub Date : 2023-01-01 DOI:10.5114/fn.2022.123516

Shuang Tian, Zhenzhen Qu, Huifang Cao, Xiaoli Niu, Qi Qiao, Bing Zhang, Lijing Jia, Weiping Wang

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引用次数: 0

Abstract

Introduction: The purpose of this study is to investigate whether Dl-3-n-Butylphthalide (NBP) has a neuroprotective effect on pilocarpine-induced epileptic (EP) rats through endoplasmic reticulum stress (ERS)-mediated apoptosis.

Material and methods: The Sprague-Dawley rats were divided into four groups: control (CON), EP, EP + NBP 60 (NBP 60 mg/kg) and EP + NBP 120 (NBP 120 mg/kg) groups. After the successful establishment of the temporal lobe EP model using the lithium-pilocarpine, the rats were given NBP for 28 consecutive days in EP + NBP 60 and EP + NBP 120 groups. Then, the spontaneous recurrent seizure (SRS) latency, SRS frequency and seizure duration were observed in each group. In order to observe the abnormal discharge of rats, the intracranial electrodes were implanted to monitor the electroencephalogram. Nissl staining was used to observe the damage to the hippocampal CA1 neurons, TUNEL staining was employed to observe hippocampal neuronal apoptosis. Western blot was used to detect the expression of ERS and ERS-mediated apoptotic proteins.

Results: NBP 60 and NBP 120 decreased SRS frequency (all p < 0.05), shortened seizure duration (all p < 0.05), and reduced the abnormal discharge of the brain. Nissl staining and TUNEL staining results show that NBP protected the hippocampal neurons from damage (all p < 0.05) and inhibited hippocampal neuronal apoptosis in EP rats (all p < 0.05). NBP 60 and NBP 120 could reduce ERS and ERS-mediated apoptotic protein expression in EP rats (all p < 0.05). In addition, the therapeutic effect of NBP on epilepsy in rats is dose-dependent. The SRS frequency of the EP + NBP 120 group was lower, and the seizure duration was shorter than in the EP + NBP 60 group (all p < 0.05), and there were more neurons in the EP + NBP 120 group than in the EP + NBP 60 group ( p < 0.05).

Conclusions: NBP had a significant neuroprotective effect in EP rats. Large doses of NBP are more effective than low doses. The mechanism may be associated with the inhibition of ERS and ERS-mediated apoptosis.

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dl -3-正丁苯酞通过抑制内质网应激对癫痫大鼠的神经保护作用。

前言:本研究旨在探讨dl -3-n-丁苯酞(NBP)是否通过内质网应激(ERS)介导的凋亡对匹罗卡品诱导的癫痫大鼠具有神经保护作用。材料与方法:将sd大鼠分为4组:对照组(CON)、EP、EP + NBP 60 (NBP 60 mg/kg)和EP + NBP 120 (NBP 120 mg/kg)组。用锂-匹罗卡品建立颞叶EP模型成功后，将大鼠分为EP + NBP 60组和EP + NBP 120组，连续给予28 d。观察各组自发性再发作(SRS)潜伏期、发作频率及持续时间。为了观察大鼠的异常放电，在大鼠脑内植入电极监测脑电图。Nissl染色观察海马CA1神经元的损伤情况，TUNEL染色观察海马神经元凋亡情况。Western blot检测ERS及ERS介导的凋亡蛋白的表达。结果:NBP 60和NBP 120降低了SRS频率(p < 0.05)，缩短了癫痫发作时间(p < 0.05)，减少了脑异常放电。Nissl染色和TUNEL染色结果显示，NBP对EP大鼠海马神经元损伤有保护作用(均p < 0.05)，对海马神经元凋亡有抑制作用(均p < 0.05)。NBP 60和NBP 120可降低EP大鼠ERS及ERS介导的凋亡蛋白表达(均p < 0.05)。此外，NBP对大鼠癫痫的治疗作用呈剂量依赖性。EP + NBP 120组的SRS频率低于EP + NBP 60组，癫痫发作持续时间短于EP + NBP 60组(p < 0.05)， EP + NBP 120组的神经元数量多于EP + NBP 60组(p < 0.05)。结论:NBP对EP大鼠有明显的神经保护作用。大剂量的NBP比小剂量更有效。其机制可能与抑制ERS和ERS介导的细胞凋亡有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Folia neuropathologica 医学-病理学

CiteScore

2.50

自引率

5.00%

发文量

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.