Department of Pediatrics, Hangzhou Red Cross Hospital, Hangzhou 310002, China.
Department of Pediatrics, Hangzhou Red Cross Hospital, Hangzhou 310002, China
Biosci Rep. 2018 Oct 31;38(5). doi: 10.1042/BSR20181206.
: Fangjing decoction is a Traditional Chinese Medicine that exhibits anticonvulsive effects in treating febrile seizures (FS). Its action mechanism and the regulation on Akt/mammalian target of rapamycin (mTOR) pathway were revealed in the present study.: FS model was established in Sprague-Dawley rats with or without Fangjing decoction treatment. On day 5, following initiation of drug treatment, seizures were monitored. Hippocampal neuron apoptosis was assessed using terminal dUTP nick end-labeling method. The levels of Bax, protein kinase B (Akt), phospho-Akt (p-Akt), mTOR, and p-mTOR proteins were analyzed using Western blotting. The content of hippocampal γ-aminobutyric acid (GABA) was measured by using ELISA assay.: Compared with the control group (=8), Fangjing decoction effectively prolonged the latency but shortened the duration of FS in rats (=8). Concomitantly, the apoptosis of hippocampal neurons, as well as Bax protein levels were also decreased in FS rats which were treated with Fangjing decoction. In addition, the Akt/mTOR signaling was found to be activated in rat hippocampus following FS, as evidenced by increased p-Akt and p-mTOR, while Fangjing decoction could inhibit the activation of Akt/mTOR signaling. Furthermore, the low GABA content in rat hippocampus following FS was significantly elevated by Fangjing decoction treatment. More importantly, SC79, a specific activator for Akt, apparently attenuated the protective effects of Fangjing decoction on FS rats.: These results suggest that Fangjing decoction protects the hippocampal neurons from apoptosis by inactivating Akt/mTOR pathway, which may contribute to mitigating FS-induced brain injury.
: 防痉汤是一种中药，具有抗惊厥作用，可用于治疗热性惊厥（FS）。本研究揭示了其作用机制和对 Akt/哺乳动物雷帕霉素靶蛋白（mTOR）通路的调节。: 在 FS 模型大鼠中建立了 Sprague-Dawley 大鼠模型，并用或不用防痉汤进行治疗。在开始用药后的第 5 天，监测癫痫发作。采用末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记法（TUNEL）评估海马神经元凋亡。采用 Western blot 法分析 Bax、蛋白激酶 B（Akt）、磷酸化 Akt（p-Akt）、mTOR 和磷酸化 mTOR（p-mTOR）蛋白水平。采用 ELISA 法测定海马γ-氨基丁酸（GABA）含量。: 与对照组（=8）相比，防痉汤能有效延长 FS 大鼠的潜伏期，但缩短 FS 的持续时间（=8）。同时，防痉汤还可降低 FS 大鼠海马神经元凋亡和 Bax 蛋白水平。此外，FS 后大鼠海马 Akt/mTOR 信号被激活，表现为 p-Akt 和 p-mTOR 增加，而防痉汤可抑制 Akt/mTOR 信号的激活。此外，FS 后大鼠海马 GABA 含量明显降低，而防痉汤治疗可显著升高其含量。更重要的是，Akt 的特异性激活剂 SC79 可明显减弱防痉汤对 FS 大鼠的保护作用。: 这些结果表明，防痉汤通过抑制 Akt/mTOR 信号通路激活，保护海马神经元免受凋亡，从而减轻 FS 引起的脑损伤。
