Pramipexole-Induced Hypothermia Reduces Early Brain Injury via PI3K/AKT/GSK3β pathway in Subarachnoid Hemorrhage rats.
Pramipexole-Induced Hypothermia Reduces Early Brain Injury via PI3K/AKT/GSK3β pathway in Subarachnoid Hemorrhage rats.
复制标题
普拉克索诱导的低温通过 PI3K/AKT/GSK3β 途径减少蛛网膜下腔出血大鼠的早期脑损伤
DOI：
10.1038/srep23817
复制
发表时间：
2016-03-30
影响因子：
4.6
通讯作者：
Chen G
中科院分区：
文献类型：
--
作者：
Ma J;Wang Z;Liu C;Shen H;Chen Z;Yin J;Zuo G;Duan X;Li H;Chen G
此前的研究表明，低温具有神经保护作用。然而，其对蛛网膜下腔出血(SAH)所致的早期脑损伤(EBI)的作用尚不清楚。本研究采用蛛网膜下腔出血(SAH)大鼠模型，研究普拉克索诱导的低温对SAH后EBI的影响及其机制。通过剂量-反应实验选择合适的普拉克索浓度和给药频率以诱导亚低温(33-36 °C)。采用Western印迹、神经行为测定、末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法(TUNEL)和荧光素B(FJB)染色等方法，检测普拉克索诱导的低温对SAH诱导的脑损伤的影响，以及控制性复温能否减弱这些影响。应用针对PI3K/AKT/GSK3β通路的抑制剂，以确定普拉克索的降温作用是否通过PI3K/AKT/GSK3β信号通路介导。结果表明，以0.25 mg/kg体重，每8 小时腹腔注射一次普拉克索，可安全、有效地维持大鼠亚低温状态。普拉克索诱导的低温以PI3K/AKT/GSK3β信号依赖的方式改善蛛网膜下腔出血所致的脑细胞死亡、血脑屏障损伤和神经行为缺陷。因此，我们可以得出结论：普拉克索诱导的低温可通过PI3K/Akt/Gsk3β信号通路有效地抑制蛛网膜下腔出血后的脑损伤。
Previous studies have shown neuroprotective effects of hypothermia. However, its effects on subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) remain unclear. In this study, a SAH rat model was employed to study the effects and mechanisms of pramipexole-induced hypothermia on EBI after SAH. Dose-response experiments were performed to select the appropriate pramipexole concentration and frequency of administration for induction of mild hypothermia (33–36 °C). Western blot, neurobehavioral evaluation, Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Fluoro-Jade B (FJB) staining were used to detect the effects of pramipexole-induced hypothermia on SAH-induced EBI, as well as to study whether controlled rewarming could attenuate these effects. Inhibitors targeting the PI3K/AKT/GSK3β pathway were administered to determine whether the neuroprotective effect of pramipexole-induced hypothermia was mediated by PI3K/AKT/GSK3β signaling pathway. The results showed that intraperitoneal injection of pramipexole at 0.25 mg/kg body weight once per 8 hours was found to successfully and safely maintain rats at mild hypothermia. Pramipexole-induced hypothermia ameliorated SAH-induced brain cell death, blood-brain barrier damage and neurobehavioral deficits in a PI3K/AKT/GSK3β signaling-dependent manner. Therefore, we may conclude that pramipexole-induced hypothermia could effectively inhibit EBI after SAH in ratsviaPI3K/AKT/GSK3β signaling pathway.