Propofol, a generally used anaesthetic in patients care, has been proven to induce neurotoxicity. Studies have shown that miR‐363‐3p was closely related to neurological dysfunction, and the up‐regulated miR‐363‐3p was recognized to be participate in propofol‐induced neurotoxicity. However, the mechanisms and functions of miR‐363‐3p in propofol‐induced neurotoxicity remain rarely reported. The aim of our research was to clarify the potential effects of miR‐363‐3p in neurotoxicity induced by propofol. SH‐SY5Y cells were treated with propofol, miR‐363‐3p inhibitor or sh‐CREB. quantitative real‐time polymerase chain reaction and western blotting were applied to detect the expression of miR‐363‐3p, CREB, Bax, Bcl‐2, cleaved caspase‐9 and cleaved caspase‐3 at the mRNA and/or protein level, respectively. The levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA) in cell supernatant were detected using different kits. Flow cytometry and MTT assay were applied for assessing the functions of miR‐363‐3p and CREB on cell ability in cellular activity and apoptotic rate. In addition, Bioinformatic analysis and luciferase assay verified the relationship between 3′‐UTR of CREB and miR‐363‐3p. Our data indicated that the cell viability decreased with the increasing propofol concentration. Bioinformatic analysis and luciferase assay suggested that 3′‐UTR of transcript of CREB might be a binding site of miR‐363‐3p, and miR‐363‐3p could negatively regulate the expression of CREB. The changes in reactive oxygen species, LDH, SOD and MDA suggested that propofol mediates oxidative stress and apoptosis via modulating miR‐363‐3p/CREB axis. Propofol induces oxidative stress and apoptosis via affecting miR‐363‐3p/CREB axis in SH‐SY5Y cells, suggesting miR‐363‐3p down‐regulation may act as a novel strategy to ameliorate the propofol‐induced neurotoxicity.

中文翻译：

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丙泊酚通过调节miR-363-3p / CREB信号转导轴在体外诱导氧化应激和细胞凋亡。

丙泊酚是患者护理中常用的麻醉剂，已被证明可诱导神经毒性。研究表明，miR-363-3p与神经功能障碍密切相关，而上调的miR-363-3p被认为参与了异丙酚诱导的神经毒性。但是，仍然很少报道miR‐363‐3p在异丙酚诱导的神经毒性中的机制和功能。我们研究的目的是阐明miR‐363-3p在异丙酚诱导的神经毒性中的潜在作用。SH-SY5Y细胞用丙泊酚，miR-363-3p抑制剂或sh-CREB处理。实时定量聚合酶链反应和Western印迹法分别在mRNA和/或蛋白水平上检测miR‐363-3p，CREB，Bax，Bcl-2，裂解的caspase-9和裂解的caspase-3的表达。乳酸脱氢酶（LDH）的水平 使用不同的试剂盒检测细胞上清液中的超氧化物歧化酶（SOD）和丙二醛（MDA）。流式细胞仪和MTT分析法用于评估miR‐363-3p和CREB对细胞活性，细胞凋亡率和细胞凋亡的功能。此外，生物信息学分析和荧光素酶测定法验证了CREB的3'-UTR与miR-363-3p之间的关系。我们的数据表明，细胞活性随丙泊酚浓度的增加而降低。生物信息学分析和萤光素酶分析表明，CREB转录本的3'-UTR可能是miR-363-3p的结合位点，而miR-363-3p可能对CREB的表达产生负调控。活性氧，LDH，SOD和MDA的变化表明，丙泊酚通过调节miR-363-3p / CREB轴来介导氧化应激和细胞凋亡。