Department of Anesthesiology, Cancer Hospital Affiliated to Harbin Medical University, 150 Haping Road (Street), NanGang District, Harbin, 150081, Heilongjiang Province, PR China.
Neurogenetics. 2024 Oct;25(4):367-375. doi: 10.1007/s10048-024-00772-w. Epub 2024 Jul 8.
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.
我们的目的是通过 TREK-1 通路探索右美托咪定对脑细胞凋亡的保护作用及其机制。40 只雄性 Sprague-Dawley 大鼠被分为四组：假手术组、脑缺血再灌注损伤组（CIRI 组）、50μg/kg 右美托咪定组和 100μg/kg 右美托咪定组。采用大脑中动脉阻塞（MCAO）大鼠模型模拟脑栓塞。原代皮质神经元用 Dex 处理 48h，部分用 100μM育亨宾盐酸盐（YOH）或 TREK-1 小干扰 RNA（siRNA）处理。苏木精-伊红（HE）染色评估神经元损伤。用细胞计数试剂盒-8（CCK8）和流式细胞术分别测量细胞活力和细胞凋亡。用 Western blot 和实时聚合酶链反应（PCR）测定 Bcl-2、Bax 和 TREK-1 的蛋白和基因表达水平。组织病理学变化表明，与 CIRI 组相比，50μg/kg 和 100μg/kg 的 Dex 处理均显著减轻了神经元损伤。YOH 处理和 Trek1 siRNA 显著降低了细胞活力（p<0.05）。TREK-1 和 Bax 的 mRNA 表达和蛋白水平显著增加，而 Bcl-2 的 mRNA 表达和蛋白水平在 CIRI 模型建立后严重降低。相反，两种浓度的 Dex 处理导致原代皮质神经元中 TREK-1 和 Bax 的表达减少，Bcl-2 的表达增加。加入 100μM YOH 和 Trek1 siRNA 逆转了 Dex 对凋亡相关基因的作用（p<0.05）。Dex 在体内和体外通过 TREK-1 通路发挥神经保护作用。
