Si Jianping, Wang Yingyan, Xu Jing, Wang Jiwen
Department of Pediatrics, The People's Hospital of Guangrao, Dongying, Shandong 257300, P.R. China.
Department of Neurology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China.
Exp Ther Med. 2020 Dec;20(6):177. doi: 10.3892/etm.2020.9307. Epub 2020 Oct 9.
The aim of the present study was to explore the potential anticonvulsant effects of β-hydroxybutyrate (BHB) in a kainic acid (KA)-induced rat epilepsy model. The KA-induced rat seizure model was established and BHB was administrated intraperitoneally at a dose of 4 mmol/kg 30 min prior to KA injection. Hippocampal tissues were then obtained 1, 3 and 7 days following KA administration, following which the expression levels of neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP) were measured using a double immunofluorescence labeling method. In addition, the contents of glutathione (GSH), γ-aminobutyric acid (GABA) and ATP were measured using ELISA. Pretreatment with BHB markedly increased the expression of NSE after KA injection compared with that in the normal saline (NS) + KA group, suggesting that the application of BHB could alleviate neuronal damage in rats. The protective effect of BHB may be associated with suppressed inflammatory responses, which was indicated by the observed inhibition of GFAP expression in rats in the BHB + KA group compared with that in the NS + KA group. It was also found that GSH and GABA contents were notably increased after the rats were pretreated with BHB compared with those in the NS + KA group. To conclude, the application of exogenous BHB can serve as a novel therapeutic agent for epilepsy.
本研究的目的是在 kainic 酸（KA）诱导的大鼠癫痫模型中探索 β-羟基丁酸（BHB）的潜在抗惊厥作用。建立 KA 诱导的大鼠癫痫发作模型，并在注射 KA 前 30 分钟以 4 mmol/kg 的剂量腹腔注射 BHB。在给予 KA 后 1、3 和 7 天获取海马组织，然后使用双重免疫荧光标记法测量神经元特异性烯醇化酶（NSE）和胶质纤维酸性蛋白（GFAP）的表达水平。此外，使用 ELISA 测量谷胱甘肽（GSH）、γ-氨基丁酸（GABA）和 ATP 的含量。与生理盐水（NS）+KA 组相比，BHB 预处理显著增加了 KA 注射后 NSE 的表达，表明应用 BHB 可减轻大鼠的神经元损伤。BHB 的保护作用可能与抑制炎症反应有关，这通过 BHB+KA 组大鼠中 GFAP 表达的抑制与 NS+KA 组相比得到证实。还发现与 NS+KA 组相比，大鼠经 BHB 预处理后 GSH 和 GABA 含量显著增加。总之，外源性 BHB 的应用可作为癫痫的一种新型治疗药物。
