Abstract：
Our objective is to explore the protective effect of Dexmedetomidine on brain apoptosis and its mechanism through TREK-1 pathway. Forty male Sprague-Dawley rats were allocated into four groups: Sham, Cerebral Ischemia/Reperfusion Injury (CIRI), 50 µg/kg Dex, and 100 µg/kg Dex. A rat model of middle cerebral artery occlusion (MCAO) was employed to simulate cerebral embolism. Primary cortical neurons were exposed to Dex for 48 h, with some receiving additional treatment with 100 µM yohimbine hydrochloride (YOH) or TREK-1 small interfering RNA (siRNA). Neuronal damage was assessed using hematoxylin and eosin (HE) staining. Cell viability and apoptosis were measured by Cell Counting Kit-8 (CCK8) and flow cytometry, respectively. Protein and gene expression levels of Bcl-2, Bax, and TREK-1 were determined by Western blot and real-time polymerase chain reaction (PCR). Histopathological changes revealed that Dex treatment at both 50 µg/kg and 100 µg/kg significantly mitigated neuronal damage compared to the CIRI group. YOH treatment and Trek1 siRNA significantly reduced cell viability (p < 0.05). The mRNA expression and protein levels of TREK-1 and Bax were remarkably increased, while mRNA expression and protein levels of Bcl-2 was seriously decreased after CIRI modeling. In contrast, Dex treatment at both concentrations led to decreased TREK-1 and Bax expression and increased Bcl-2 expression in primary cortical neurons. Addition of 100 µM YOH and Trek1 siRNA reversed the effects of Dex on apoptosis-related genes (p < 0.05). Dex exerts neuroprotective effects through the TREK-1 pathway in vivo and in vitro.
摘要：
我们的目的是探讨右美托咪定通过TREK-1通路对脑细胞凋亡的保护作用及其机制。将40只雄性Sprague-Dawley大鼠分为四组：假，脑缺血/再灌注损伤(CIRI),50µg/kgDex,和100µg/kgDex.采用大鼠大脑中动脉闭塞（MCAO）模型模拟脑栓塞。原代皮质神经元暴露于Dex48小时，其中一些接受100μM盐酸育亨宾（YOH）或TREK-1小干扰RNA（siRNA）的额外治疗。使用苏木精和伊红(HE)染色评估神经元损伤。通过细胞计数试剂盒-8（CCK8）和流式细胞术测量细胞活力和凋亡，分别。Bcl-2、Bax蛋白和基因表达水平,通过蛋白质印迹和实时聚合酶链反应（PCR）测定TREK-1。组织病理学变化表明，与CIRI组相比，Dex治疗在50µg/kg和100µg/kg下均显着减轻了神经元损伤。YOH处理和Trek1siRNA显著降低细胞活力(p<0.05)。TREK-1和Bax的mRNA表达和蛋白水平显著升高,CIRI建模后，Bcl-2的mRNA表达和蛋白水平严重下降。相比之下,两种浓度的Dex处理导致原代皮质神经元中TREK-1和Bax表达降低和Bcl-2表达增加。添加100μMYOH和Trek1siRNA可逆转Dex对凋亡相关基因的影响（p<0.05）。Dex通过TREK-1途径在体内和体外发挥神经保护作用。
