Department of Physiology, College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University, Dalian, 116044, China.
Department of Physiology, College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University, Dalian, 116044, China; National-Local Joint Engineering Research Center for Drug-Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian, 116044, China.
Eur J Pharmacol. 2024 Sep 5;978:176704. doi: 10.1016/j.ejphar.2024.176704. Epub 2024 Jun 1.
Finding new and effective natural products for designing antiepileptic drugs is highly important in the scientific community. The scorpion venom heat-resistant peptide (SVHRP) was purified from Buthus martensii Karsch scorpion venom, and subsequent analysis of the amino acid sequence facilitated the synthesis of a peptide known as scorpion venom heat-resistant synthesis peptide (SVHRSP) using a technique for peptide synthesis. Previous studies have demonstrated that the SVHRSP can inhibit neuroinflammation and provide neuroprotection. This study aimed to investigate the antiepileptic effect of SVHRSP on both acute and chronic kindling seizure models by inducing seizures in male rats through intraperitoneal administration of pentylenetetrazole (PTZ). Additionally, an N-methyl-D-aspartate (NMDA)-induced neuronal injury model was used to observe the anti-excitotoxic effect of SVHRSP in vitro. Our findings showed that treatment with SVHRSP effectively alleviated seizure severity, prolonged latency, and attenuated neuronal loss and glial cell activation. It also demonstrated the prevention of alterations in the expression levels of NMDA receptor subunits and phosphorylated p38 MAPK protein, as well as an improvement in spatial reference memory impairment during Morris water maze (MWM) testing in PTZ-kindled rats. In vitro experiments further revealed that SVHRSP was capable of attenuating neuronal action potential firing, inhibiting NMDA receptor currents and intracellular calcium overload, and reducing neuronal injury. These results suggest that the antiepileptic and neuroprotective effects of SVHRSP may be mediated through the regulation of NMDA receptor function and expression. This study provides new insight into therapeutic strategies for epilepsy.
从东亚钳蝎（Buthus martensii Karsch）蝎毒中分离纯化出一种新型热稳定蝎毒素（SVHRP），通过氨基酸序列分析，设计并合成了蝎毒素热稳定合成肽（SVHRSP）。前期研究表明，SVHRSP 具有抑制神经炎症和神经保护作用。本研究旨在探讨 SVHRSP 对急性和慢性点燃癫痫模型的抗癫痫作用。通过腹腔注射戊四氮（PTZ）诱导雄性大鼠癫痫发作，观察 SVHRSP 的作用；通过 NMDA 诱导的神经元损伤模型观察 SVHRSP 的体外抗兴奋毒性作用。结果显示，SVHRSP 可有效减轻癫痫发作严重程度，延长潜伏期，减轻神经元丢失和胶质细胞激活。SVHRSP 还可预防 NMDA 受体亚基和磷酸化 p38MAPK 蛋白表达水平的改变，改善 PTZ 点燃大鼠在 Morris 水迷宫（MWM）测试中的空间参考记忆障碍。体外实验进一步表明，SVHRSP 可抑制神经元动作电位发放，抑制 NMDA 受体电流和细胞内钙超载，减轻神经元损伤。这些结果提示，SVHRSP 的抗癫痫和神经保护作用可能与调节 NMDA 受体功能和表达有关。本研究为癫痫的治疗策略提供了新的思路。
