circRNA_34414/miR-6960a-5p/SIRT3 轴通过老年小鼠 CA1 Vglut1+神经元在术后谵妄中的作用。

Role of the circRNA_34414/miR-6960a-5p/SIRT3 axis in postoperative delirium via CA1 Vglut1+ neurons in older mice.

机构信息

Jiangsu Province Key Laboratory of Anesthesiology/NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, China.

Department of Anesthesiology, Qidong People's Hospital/Qidong Liver Cancer Institute/Affiliated Qidong Hospital of Nantong University, Nantong, China.

出版信息

CNS Neurosci Ther. 2024 Aug;30(8):e14902. doi: 10.1111/cns.14902.

DOI:10.1111/cns.14902

PMID:39138637

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11322041/

Abstract

AIMS

Postoperative delirium (POD) is a common neurological complication in elderly patients after anesthesia/surgery. The main purpose of this study is to explore the effect of circRNA-targeted miRNA regulating SIRT3 on mitochondrial function through ceRNA mechanism under the surgical model of tibial fracture and to further explore the potential mechanism of postoperative delirium mediated by circRNA, so as to provide new ideas for clinical diagnosis and prevention of POD.

METHODS

The surgical model of tibial fracture under sevoflurane anesthesia caused acute delirium-like behavior in elderly mice. We observed that the decrease of SIRT3 and mitochondrial dysfunction was related to POD, and miRNA and circRNA (circRNA_34414) related to SIRT3 were further studied. Through luciferase and RAP, we observed that circRNA_34414, as a miRNA sponge, was involved in the regulation of SIRT3 expression.

RESULTS

Postoperative delirium in elderly mice showed decreased expression of hippocampal circRNA_34414, increased expression of miR-6960-5p, decreased expression of SIRT3, and impaired mitochondrial membrane potential. Overexpression of circRNA_34414, or knockdown of miR-6960-5p, or overexpression of SIRT3 in hippocampal CA1 glutamatergic neurons significantly upregulated hippocampal SIRT3 expression, increased mitochondrial membrane potential levels, and significantly ameliorated postoperative delirium in aged mice; CircRNA_34414 ameliorates postoperative delirium in mice, possibly by targeting miR-6960-5p to upregulate SIRT3.

CONCLUSIONS

CircRNA_34414 is involved in the improvement of postoperative delirium induced by anesthesia/surgery by upregulating SIRT3 via sponging miR-6960-5p.

摘要

目的

术后谵妄（POD）是老年患者麻醉/手术后常见的神经并发症。本研究的主要目的是通过 ceRNA 机制探讨circRNA 靶向 miRNA 调节 SIRT3 对线粒体功能的影响，进一步探讨circRNA 介导术后谵妄的潜在机制，为临床诊断和预防 POD 提供新思路。

方法

七氟醚麻醉下胫骨骨折手术模型引起老年小鼠急性谵妄样行为。我们观察到 SIRT3 减少和线粒体功能障碍与 POD 相关，并进一步研究了与 SIRT3 相关的 miRNA 和 circRNA（circRNA_34414）。通过荧光素酶和 RAP，我们观察到 circRNA_34414 作为 miRNA 海绵，参与了 SIRT3 表达的调节。

结果

老年小鼠术后谵妄表现为海马 circRNA_34414 表达降低，miR-6960-5p 表达增加，SIRT3 表达降低，线粒体膜电位受损。海马 CA1 谷氨酸能神经元中 circRNA_34414 的过表达，或 miR-6960-5p 的敲低，或 SIRT3 的过表达，均显著上调海马 SIRT3 表达，增加线粒体膜电位水平，显著改善老年小鼠术后谵妄；circRNA_34414 通过靶向 miR-6960-5p 上调 SIRT3 改善小鼠术后谵妄。