Department of Anesthesia, Shandong Provincial Hospital, Shandong First Medical University, No.324, Jingwu Road, Huaiyin District, Jinan, Shandong, 250021, China.
Appl Biochem Biotechnol. 2024 Aug;196(8):4849-4861. doi: 10.1007/s12010-023-04768-4. Epub 2023 Nov 18.
Propofol can induce neuroapoptosis. It has been reported that dexmedetomidine (DEX) has a protective effect on propofol-induced neuroapoptosis, but the specific mechanism needs to be further explored to provide a theoretical basis for their combined use.
We aimed to explore the neuroprotective effect of DEX on primary cortical neurons treated by propofol and to elucidate the underlying mechanistic pathways.
Cortical neurons were isolated from fetal rats and treated with propofol. MTT assays were performed to detect cell viability, α-tubulin immunofluorescent assays were conducted to observe cell abnormalities, and c-caspase3 immunofluorescent assays and flow cytometry were performed to examine cell apoptosis. Further, neurons were cotreated with propofol and DEX to study DEX's neuroprotective effects on propofol-caused neuronal injuries. Finally, the α-adrenoceptor was knocked out and/or the Akt activator (SC-79) was added to cells co-treated with propofol and DEX. The expression levels of Akt-IKK-NF-κB pathway-related proteins were detected by western blot.
Propofol decreased cell viability in a dose-dependent manner, triggered apoptosis, caused morphological abnormalities and down-regulated the phosphorylation levels of Akt, IKK, NF-κB and IκB in cortical neurons. DEX ameliorated the decrease of cell viability, alleviated neuronal apoptosis and promoted the downregulated expression levels of p-Akt, IKK, NF-κB, and IκB proteins which had been induced by propofol treatment. Western blot findings following the transfection of α-siRNA and the addition of SC-79 suggested that DEX's neuroprotective functions arose from the stimulation of α-adrenoceptors to activate the Akt-IKK-NF-κB signal pathway.
DEX protected neurons against propofol-induced apoptosis via activation of the Akt-IKK-NF-κB signal pathway through α-adrenoceptors.
丙泊酚可诱导神经细胞凋亡。有报道称，右美托咪定（DEX）对丙泊酚诱导的神经细胞凋亡具有保护作用，但具体机制尚需进一步探讨，为两者联合应用提供理论依据。
探讨 DEX 对丙泊酚处理的原代皮质神经元的神经保护作用，并阐明其潜在的作用机制。
分离胎鼠皮质神经元并给予丙泊酚处理。采用 MTT 比色法检测细胞活力，α-微管蛋白免疫荧光法观察细胞形态学改变，c-caspase3 免疫荧光法和流式细胞术检测细胞凋亡。进一步给予皮质神经元丙泊酚和 DEX 共处理，研究 DEX 对丙泊酚诱导的神经元损伤的神经保护作用。最后，敲除α-肾上腺素能受体或加入 Akt 激活剂（SC-79），检测丙泊酚和 DEX 共处理的细胞中 Akt-IKK-NF-κB 通路相关蛋白的表达水平。
丙泊酚呈剂量依赖性降低细胞活力，触发细胞凋亡，导致皮质神经元形态异常，并下调 Akt、IKK、NF-κB 和 IκB 的磷酸化水平。DEX 可改善丙泊酚处理引起的细胞活力下降，减轻神经元凋亡，并促进 Akt、IKK、NF-κB 和 IκB 蛋白的下调表达。转染α-siRNA 和加入 SC-79 后的 Western blot 结果表明，DEX 的神经保护作用源于通过α-肾上腺素能受体刺激激活 Akt-IKK-NF-κB 信号通路。
DEX 通过激活 Akt-IKK-NF-κB 信号通路，通过α-肾上腺素能受体保护神经元免受丙泊酚诱导的凋亡。
