Si Pei-Pei, Zhen Jun-Li, Cai Yun-Lei, Wang Wen-Jing, Wang Wei-Ping
Key Laboratory of Neurology of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050071, PR China.
Key Laboratory of Neurology of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050071, PR China.
Neurosci Lett. 2016 Apr 8;618:19-24. doi: 10.1016/j.neulet.2016.02.056. Epub 2016 Mar 3.
There are numerous mechanisms by which the brain generates seizures. It is well known that oxidative stress plays a pivotal role in status epilepticus (SE). Salidroside (SDS) extracted from Rhodiola rosea L. shows multiple bioactive properties, such as neuroprotection and antioxidant activity in vitro and in vivo. This study explored the role of SDS in kainic acid (KA)-induced SE and investigated the underlying mechanism. Latency to SE increased in the SDS-pretreated mice compared to the KA group, while the percentage of incidence of SE was significantly reduced. These results suggested that pretreatment with SDS not only delayed SE, but it also decreased the incidence of SE induced by KA. KA increased MDA level and reduced the production of SOD and GSH at multiple timepoints after KA administration. SDS inhibited the change of MDA, SOD and GSH induced by KA prior to SE onset, indicating that SDS protects against KA-induced SE via suppressing oxidative stress. Based on these results, we investigated the possible molecular mechanism of SDS. Pretreatment with SDS reversed the KA-induced decrease in AMP-activated protein kinase (AMPK); increased the sirtuin 1 (SIRT1) deacetylase activity in KA-treated mice, which had no demonstrable effect on SIRT1 mRNA and protein; and suppressed the KA-induced increase in Ace-FoxO1. These results showed that AMPK/SIRT1/FoxO1 signaling is possibly the molecular mechanism of neuroprotection by SDS.
大脑产生癫痫发作的机制众多。众所周知，氧化应激在癫痫持续状态（SE）中起关键作用。从红景天中提取的红景天苷（SDS）具有多种生物活性，如在体外和体内均具有神经保护和抗氧化活性。本研究探讨了SDS在 kainic 酸（KA）诱导的 SE 中的作用，并研究了其潜在机制。与 KA 组相比，SDS 预处理小鼠的 SE 潜伏期延长，而 SE 的发生率显著降低。这些结果表明，SDS 预处理不仅延迟了 SE，还降低了 KA 诱导的 SE 的发生率。KA 给药后多个时间点，KA 增加了 MDA 水平，降低了 SOD 和 GSH 的产生。SDS 在 SE 发作前抑制了 KA 诱导的 MDA、SOD 和 GSH 的变化，表明 SDS 通过抑制氧化应激来预防 KA 诱导的 SE。基于这些结果，我们研究了 SDS 可能的分子机制。SDS 预处理逆转了 KA 诱导的 AMP 激活蛋白激酶（AMPK）的降低；增加了 KA 处理小鼠中沉默调节蛋白 1（SIRT1）的去乙酰化酶活性，而对 SIRT1 mRNA 和蛋白没有明显影响；并抑制了 KA 诱导的 Ace-FoxO1 的增加。这些结果表明，AMPK/SIRT1/FoxO1 信号通路可能是 SDS 发挥神经保护作用的分子机制。
