Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, P.R. China.
Department of Neurology, Shijiazhuang People's Hospital, Shijiazhuang, Hebei, P.R. China.
Folia Neuropathol. 2023;61(2):185-195. doi: 10.5114/fn.2022.123516.
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.
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.
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).
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.
本研究旨在探讨 Dl-3-正丁基苯酞（NBP）是否通过内质网应激（ERS）介导的细胞凋亡对匹罗卡品诱导的癫痫（EP）大鼠具有神经保护作用。
将 Sprague-Dawley 大鼠分为四组：对照组（CON）、EP 组、EP+NBP60（NBP60mg/kg）组和 EP+NBP120（NBP120mg/kg）组。采用锂-匹罗卡品成功建立颞叶 EP 模型后，EP+NBP60 和 EP+NBP120 组大鼠连续 28 天给予 NBP。然后观察各组大鼠的自发性复发发作（SRS）潜伏期、SRS 频率和发作持续时间。为观察大鼠的异常放电情况，植入颅内电极监测脑电图。尼氏染色观察海马 CA1 神经元损伤，TUNEL 染色观察海马神经元凋亡。Western blot 检测 ERS 及 ERS 介导的凋亡蛋白表达。
NBP60 和 NBP120 降低 SRS 频率（均 p<0.05），缩短发作持续时间（均 p<0.05），减少脑异常放电。尼氏染色和 TUNEL 染色结果显示，NBP 可保护海马神经元免受损伤（均 p<0.05），抑制 EP 大鼠海马神经元凋亡（均 p<0.05）。NBP60 和 NBP120 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+NBP120 组 SRS 频率较低，发作持续时间短于 EP+NBP60 组（均 p<0.05），EP+NBP120 组神经元多于 EP+NBP60 组（ p<0.05）。
NBP 对 EP 大鼠具有显著的神经保护作用。大剂量 NBP 比低剂量更有效。其机制可能与抑制 ERS 和 ERS 介导的细胞凋亡有关。
