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选择性PI3K抑制剂度维利西布对戊四氮诱导惊厥动物模型癫痫活动的影响

Effect of Duvelisib, a Selective PI3K Inhibitor on Seizure Activity in Pentylenetetrazole-Induced Convulsions Animal Model.

作者信息

Abdolrahmani Mahnaz, Mirazi Naser, Hosseini Abdolkarim

机构信息

Department of Biology, Faculty of Basic Sciences, Bu-Ali Sina University, Hamedan, Iran.

Department of Animal Sciences and Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.

出版信息

Neurosci Insights. 2023 Sep 14;18:26331055231198013. doi: 10.1177/26331055231198013. eCollection 2023.

Abstract

Epilepsy is one of the most common neurological diseases, which is caused by abnormal brain activity. A wide variety of studies have shown the importance of the phosphatidylinositol-3-kinase (PI3K) signaling pathway in epilepsy pathogenesis. Duvelisib (DUV) is a selective inhibitor of PI3K. The present study investigated the anticonvulsant potential of DUV in a rat model of pentylenetetrazole (PTZ)-induced convulsions. Male Wistar rats (200-250 g, 8 weeks old) were injected intraperitoneally (IP) with DUV at different doses of 5 and 10 mg/kg, or vehicle 30 minutes prior to PTZ (70 mg/kg, IP) treatment. Based on Racine's scale, behavioral seizures were assessed. The results showed that pretreatment with DUV prolonged the seizure stages according to the Racine scale, significantly decreased the duration of general tonic-clonic seizure and reduced the number of myoclonic jerks ( < .05). In conclusion, we found that PI3K antagonist DUV significantly reduced PTZ-induced seizures, indicating that DUV exerts an anticonvulsant effect by inhibiting PI3K signaling pathway.

摘要

癫痫是最常见的神经系统疾病之一,由大脑活动异常引起。各种各样的研究表明磷脂酰肌醇-3-激酶(PI3K)信号通路在癫痫发病机制中的重要性。度维利西布(DUV)是一种PI3K选择性抑制剂。本研究在戊四氮(PTZ)诱导惊厥的大鼠模型中研究了DUV的抗惊厥潜力。雄性Wistar大鼠(200-250克,8周龄)在PTZ(70毫克/千克,腹腔注射)治疗前30分钟腹腔注射不同剂量(5和10毫克/千克)的DUV或赋形剂。根据拉辛量表评估行为性癫痫发作。结果表明,DUV预处理根据拉辛量表延长了癫痫发作阶段,显著缩短了全身强直阵挛性发作的持续时间并减少了肌阵挛抽搐的次数(<0.05)。总之,我们发现PI3K拮抗剂DUV显著减少了PTZ诱导的癫痫发作,表明DUV通过抑制PI3K信号通路发挥抗惊厥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7a/10503276/c7bab6c8990d/10.1177_26331055231198013-fig1.jpg

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