LncRNA Riken Attenuated Sevoflurane-Induced Neuroinflammation by Regulating the MicroRNA-101a/MKP-1/JNK Pathway
LncRNA Riken Attenuated Sevoflurane-Induced Neuroinflammation by Regulating the MicroRNA-101a/MKP-1/JNK Pathway
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LncRNA Riken 通过调节 MicroRNA-101a/MKP-1/JNK 通路减轻七氟烷诱导的神经炎症
DOI：
10.1007/s12640-021-00443-w
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发表时间：
2021-11-26
影响因子：
3.7
通讯作者：
Zheng, Hui
中科院分区：
文献类型：
--
作者：
Hou, Qi;Li, Shuai;Zheng, Hui
儿童麻醉诱导使其安全性成为最重要的全球健康问题之一。神经炎症导致年轻人麻醉诱导的神经毒性。然而，麻醉诱导的神经毒性的机制尚未建立。在本研究中，用七氟烷处理的小鼠海马和N2 A细胞中的白细胞介素（IL）-6水平增加，长非编码RNA（LncRNA）Riken足以降低七氟烷诱导的神经毒性和炎性细胞因子IL-6的水平。RNA pull-down测定证实miR-101 a与N2 A细胞中的lncRNA Riken结合。此外，miR-101 a阻断了lncRNA Riken对麻醉诱导的神经炎症的保护作用。这些数据表明lncRNA理研通过与microRNA-101 a相互作用来减弱麻醉诱导的神经炎症。最后，我们还证明了MAPK磷酸酶1（MKP-1）是miR-101 a的下游靶点，lncRNA Riken可以调节MKP-1的表达; JNK信号转导途径与七氟烷诱导的IL-6分泌有关。我们的研究结果表明，lncRNA Riken减轻了七氟醚诱导的神经毒性作用，lncRNA Riken/miR-101 a/MKP-1/JNK轴在认知障碍中起着重要作用。
The induction of anesthesia in children makes its safety one of the most important global health problems. Neuroinflammation contributes to anesthesia-induced neurotoxicity in young individuals. However, the mechanisms underlying anesthesia-induced neurotoxicity have not been established. In this study, the level of interleukin (IL)-6 in the hippocampus of mice and N2A cells treated with sevoflurane was increased, and long noncoding RNA (LncRNA) Riken was sufficient to decrease sevoflurane-induced neurotoxicity, and the level of inflammatory cytokine IL-6. The RNA pull-down assay verified that miR-101a was bound to lncRNA Riken in N2A cells. In addition, miR-101a blocked the protective effect of lncRNA Riken on anesthesia-induced neuroinflammation. These data suggest that lncRNA Riken attenuated anesthesia-induced neuroinflammation by interacting with microRNA-101a. Finally, we also demonstrated that MAPK phosphatase 1 (MKP-1) was a downstream target of miR-101a, and lncRNA Riken can regulate the expression of MKP-1; the JNK signal transduction pathway has been implicated in sevoflurane-induced IL-6 secretion. Our findings demonstrated that lncRNA Riken alleviated the sevoflurane-induced neurotoxic effects, and the lncRNA Riken/miR-101a/MKP-1/JNK axis plays an important role in the cognitive disorder.