槲皮素可通过调节miR-138-5p/LCN2改善麻醉诱导的神经炎症和认知功能障碍。

Quercetin can improve anesthesia induced neuroinflammation and cognitive dysfunction by regulating miR-138-5p/ LCN2.

作者信息

Lou Linjie, Yu Wanning, Cheng Ying, Lin Quan, Jiang Yanyan, Wang Dalong, Che Lei, Du Meiqing, Wang Shuai, Zhen Haining

机构信息

Department of Traditional Chinese Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.

Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China.

出版信息

BMC Anesthesiol. 2025 Jan 10;25(1):21. doi: 10.1186/s12871-024-02876-0.

DOI:10.1186/s12871-024-02876-0

PMID:39794698

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11720507/

Abstract

BACKGROUND

Anesthesia can lead to functional cognitive impairment, which can seriously affect postoperative recovery. To investigate the effect and mechanism of quercetin (Que) in anesthetized rats, the study provided a new therapeutic idea for the prevention of cognitive dysfunction caused by anesthesia.

METHODS

Cognitively impaired rats were constructed using Isoflurane (ISO) anesthesia and treated with Que. The capacity of the rats to learn and remember was tested using the Morris water maze test. Rat hippocampal tissues were collected and analyzed for inflammatory factor concentration and miR-138-5p expression using ELISA and qRT-PCR, respectively, and the targeting link between miR-138-5p and LCN2 was verified by dual luciferase reporter.

RESULTS

Que treatment was found to improve ISO-induced cognitive dysfunction and inhibit the level of hippocampal inflammatory factors in rats. miR-138-5p was down-regulated in rats with cognitive dysfunction, while Que treatment increased miR-138-5p expression. The study found that knockdown miR-138-5p can reverse the positive effects of Que therapy, aggravate cognitive dysfunction, and promote the secretion of TNF-α, IL-1β, and IL-6 in the hippocampus. In addition, LCN2, a target gene of miR-138-5p, was significantly up-regulated in the hippocampus after ISO induction.

CONCLUSION

Que may inhibit ISO-induced hippocampal neuroinflammation and ameliorate functional cognitive deficits in rats by modulating miR-138-5p/ LCN2.

摘要

背景

麻醉可导致功能性认知障碍，严重影响术后恢复。为研究槲皮素（Que）对麻醉大鼠的影响及作用机制，本研究为预防麻醉所致认知功能障碍提供了新的治疗思路。

方法

采用异氟烷（ISO）麻醉构建认知功能障碍大鼠模型，并给予Que治疗。采用Morris水迷宫试验检测大鼠的学习记忆能力。分别收集大鼠海马组织，采用ELISA法检测炎症因子浓度，qRT-PCR法检测miR-138-5p表达，并通过双荧光素酶报告基因验证miR-138-5p与LCN2之间的靶向关系。

结果

发现Que治疗可改善ISO诱导的大鼠认知功能障碍，并抑制海马炎症因子水平。miR-138-5p在认知功能障碍大鼠中表达下调，而Que治疗可增加miR-138-5p表达。研究发现，敲低miR-138-5p可逆转Que治疗的积极作用，加重认知功能障碍，并促进海马中TNF-α、IL-1β和IL-6的分泌。此外，miR-138-5p的靶基因LCN2在ISO诱导后海马中显著上调。