Department of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, China.
Department of Anesthesiology, Shanghai Sixth People's Hospital East Affiliated to Shanghai University of Medicine & Health Sciences, China.
Neurosci Lett. 2021 Jun 11;755:135897. doi: 10.1016/j.neulet.2021.135897. Epub 2021 Apr 16.
In the present study, the regulation mechanism of NAA10 (N-Alpha-Acetyltransferase 10) in sevoflurane preconditioning induced neuroprotective effect was explored.
Firstly, si-NAA10 or negative control (NC) were constructed for cell transfection and injected into intracerebroventricular of rats. Oxygen-glucose deprivation/reperfusion (OGD/R) model in vitro and middle cerebral artery occlusion (MCAO) model in vivo were established to simulate cerebral I/R injury. QRT-PCR analysis and western blotting assay were performed to assess the expression of NAA10. TTC staining, neurological evaluation and cell counting kit-8 (CCK-8) were performed to evaluate the effect of NAA10 on sevoflurane induced neuroprotection. TUNEL assay and flow cytometry were used to detect the apoptosis in vivo and in vitro.
It showed that sevoflurane preconditioning increased the expression of NAA10 in MCAO rats. TTC staining, TUNEL assay and neurological evaluation results suggested that si-NAA10 attenuated the neuroprotective effect of sevoflurane preconditioning against MCAO. CCK-8 assay, flow cytometry, qRT-PCR and western blot results showed that NAA10 mediated sevoflurane preconditioning-induced neuroprotection in vitro. Furthermore, western blot results showed that down-regulation of NAA10 could reverse the attenuation of ERK1/2 phosphorylation induced by sevoflurane preconditioning in vivo or in vitro.
Down-regulation of NAA10 regulated ERK1/2 phosphorylation mediating sevoflurane preconditioning induced neuroprotective effects. The results revealed the regulatory mechanism of NAA10 in the neuroprotective effect of sevoflurane preconditioning.
本研究旨在探讨 NAA10（N-乙酰转移酶 10）在七氟醚预处理诱导神经保护作用中的调节机制。
首先构建 si-NAA10 或阴性对照（NC）用于细胞转染，并注射到大鼠侧脑室。体外建立氧葡萄糖剥夺/再灌注（OGD/R）模型和体内建立大脑中动脉闭塞（MCAO）模型，模拟脑 I/R 损伤。采用 QRT-PCR 分析和 Western blot 检测 NAA10 的表达。TTC 染色、神经功能评估和细胞计数试剂盒-8（CCK-8）检测评估 NAA10 对七氟醚诱导的神经保护作用。TUNEL 检测和流式细胞术用于检测体内和体外的细胞凋亡。
七氟醚预处理增加了 MCAO 大鼠中 NAA10 的表达。TTC 染色、TUNEL 检测和神经功能评估结果表明，si-NAA10 减弱了七氟醚预处理对 MCAO 的神经保护作用。CCK-8 检测、流式细胞术、qRT-PCR 和 Western blot 结果表明，NAA10 介导了七氟醚预处理诱导的体外神经保护作用。此外，Western blot 结果表明，下调 NAA10 可以逆转七氟醚预处理体内或体外诱导的 ERK1/2 磷酸化的减弱。
下调 NAA10 调节 ERK1/2 磷酸化，介导七氟醚预处理诱导的神经保护作用。该结果揭示了 NAA10 在七氟醚预处理诱导的神经保护作用中的调节机制。
