目的 探讨miR-181a对七氟烷诱导海马神经元凋亡的影响及其机制。 方法 验证miR-181a与沉默信息调节因子1（silent information regulator1，sirt1）的关系，检测七氟烷对海马神经元中miR-181a表达及细胞凋亡的影响；将海马神经元转染后用3%七氟烷处理4 h，分为空白组、miR-NC组、miR-181a组、anti-miR-NC组、anti-miR-181a组、（anti-miR-NC+si-NC）组、（anti-miR-181a+si-NC）组、（anti-miR-181a+si-sirt1）组，检测各组细胞中sirt1、核因子κB（NF-κB）、sirt1蛋白、miR-181a表达及细胞凋亡情况；体内实验检测七氟烷处理或同时抑制miR-181a和sirt1表达后海马组织中神经元凋亡变化。 结果 miR-181a靶向调控sirt1表达；七氟烷使海马神经元中miR-181a表达及细胞凋亡率升高（P<0.05）；上调miR-181a抑制sirt1蛋白表达，促进NF-κB蛋白表达，而抑制miR-181a呈相反趋势（P<0.05）；体内与体外实验均证实沉默sirt1可减弱下调miR-181a对七氟烷诱导的海马神经元凋亡的抑制作用。 结论 沉默miR-181a通过激活七氟烷诱导的海马神经元中sirt1/NF-κB通路，抑制海马神经元凋亡。
Abstract
Objective To explore the effect of miR-181a on the apoptosis of hippocampal neurons induced by sevoflurane and its mechanism. Methods The relationship between miR-181a and silent information regulator 1 (sirt1) was verified. The effect of sevoflurane on miR-181a expression and apoptosis in hippocampal neurons was detected. Hippocampal neurons were transfected with 3% sevoflurane Alkane treatment for 4 h. They were divided into the following group: a blank group, a miR-NC group, a miR-181a group, an anti-miR-NC group, an anti-miR-181a group, an anti-miR-NC+si-NC group, an anti-miR-181a +si-NC group and an anti-miR-181a+si-sirt1 group. The expression of sirt1, nuclear factor kappa B (NF-κB), sirt1 protein, miR-181a and apoptosis of cells in each group were detected. The changes of neuronal apoptosis in hippocampus were detected after sevoflurane treatment or simultaneous inhibition of miR-181a and sirt1 expression by in vivo experiments. Results miR-181a regulated the expression of sirt1 by targeting. After sevoflurane treatment, the expression of miR-181a and the apoptosis rate in hippocampal neurons increased (P<0.05). Up-regulation of miR-181a inhibited the expression of sirt1 protein and promoted the expression of NF-κB protein, while inhibiting miR-181a showed the opposite trend (P<0.05). In vivo and in vitro experiments confirmed that silencing sirt1 attenuated the inhibitory effect of down-regulated miR-181a on sevoflurane-induced apoptosis in hippocampal neurons. Conclusions Silencing miR-181a inhibits hippocampal neuronal apoptosis by activating the sirt1/NF-κB pathway in hippocampal neurons treated with sevoflurane.
关键词
七氟烷 /
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海马神经元 /
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沉默信息调节因子1 /
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凋亡
Key words
Sevoflurane /
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Hippocampal neurons /
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Silent information regulator 1 /
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Apoptosis
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