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七氟醚通过损害胰岛素样生长因子受体信号通路影响记忆。

Sevoflurane Affects Memory Through Impairing Insulin-Like Growth Factor Receptor Signaling.

机构信息

Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Neurology, Shanghai Changzheng Hospital, the Second Military Medical University, Shanghai, China.

出版信息

J Alzheimers Dis. 2019;71(3):825-832. doi: 10.3233/JAD-190596.

Abstract

Administration of sevoflurane (SEVO) may induce learning and memory deficits, which increases the chances of developing Alzheimer's disease. Here, we studied the effects of SEVO exposure on rats with a focus on the role of insulin-like growth factor (IGF) signaling. SEVO exposure significantly increased neuron cell apoptosis, and caused poor performance of the rats in behavior tests, by suppressing IGF-1 receptor (IGF1R). Bioinformatic analysis predicted microRNA(miR)-223-3p as an IGF1R-binding miRNA, the level of which increased in neurons after exposure to SEVO. In vitro, miR-223-3p suppressed the translation of IGF1R in neural cells. Moreover, transfection with antisense of miR-223-3p significantly attenuated SEVO exposure-induced neuron cell apoptosis. Taken together, these data suggest that SEVO-induced miR-223-3p upregulation suppresses IGF1R to impair IGF signaling, which subsequently leads to learning and memory impairments.

摘要

七氟醚(SEVO)的管理可能会导致学习和记忆缺陷,从而增加患阿尔茨海默病的几率。在这里,我们研究了 SEVO 暴露对大鼠的影响,重点关注胰岛素样生长因子(IGF)信号的作用。SEVO 暴露显著增加神经元细胞凋亡,并通过抑制 IGF-1 受体(IGF1R)导致大鼠在行为测试中的表现不佳。生物信息学分析预测 microRNA(miR)-223-3p 是一种 IGF1R 结合 miRNA,其在神经元暴露于 SEVO 后水平增加。在体外,miR-223-3p 抑制神经细胞中 IGF1R 的翻译。此外,转染反义 miR-223-3p 可显著减轻 SEVO 暴露诱导的神经元细胞凋亡。总之,这些数据表明,SEVO 诱导的 miR-223-3p 上调抑制 IGF1R 以损害 IGF 信号,进而导致学习和记忆障碍。

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