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miRNA-124-3p 靶向 LPIN1 减轻老龄大鼠体外循环围术期神经认知障碍模型中的炎症和细胞凋亡

miRNA-124-3p targeting of LPIN1 attenuates inflammation and apoptosis in aged male rats cardiopulmonary bypass model of perioperative neurocognitive disorders.

机构信息

Department of Anesthesiology, Hospital (T.C.M) Affiliated to Southwest Medical University, Luzhou, Sichuan Province 646000, China.

Department of Anesthesiology, Hospital (T.C.M) Affiliated to Southwest Medical University, Luzhou, Sichuan Province 646000, China.

出版信息

Exp Gerontol. 2021 Nov;155:111578. doi: 10.1016/j.exger.2021.111578. Epub 2021 Oct 1.

DOI:10.1016/j.exger.2021.111578
PMID:34601076
Abstract

Perioperative neurocognitive disorder (PND) is recently recommended to define the cognitive decrease during the perioperative period. However, the disease's underlying mechanisms remain unclear. MicroRNAs (miRNAs) are noncoding RNAs that play a vital role in regulating neuroregeneration and neuronal apoptosis. In this study, miR-124-3p was significantly reduced in the PND rat model after a cardiopulmonary bypass (CPB) procedure. MicroRNA-124 (miR-124)-3p-overexpressed lentivirus was constructed and injected via the intracerebroventricular method before CPB. Morris Water Maze test (WMW) and the Open-Field test (OFT) were used to measure behavior changes, data shows decline of cognitive function of rats after CPB. PND rats expressed higher Aβ and p-Tau Protein by using immunohistochemistry (IHC) analyses and Enzyme-Linked Immune Sorbent Assay (ELISA). Moreover, the results of IHC, ELISA, Western Blot analysis (WB) and Terminal-deoxynucleotidyl Transferase Mediated Nick End Labeling Assay (TUNEL) showed CPB procedure induced inflammation and apoptosis in rats with PND. The data also revealed the protective function of miR-124-3p overexpression against PND in relieving inflammation, cell apoptosis, and alleviating repaired cognitive function. Moreover, miR-124-3p was predicted by directly targeting LPIN1. This study gives a novel viewpoint that miR-124-3p could improve the state of PND via modulating LPIN1, therefore providing a new strategy for preventing and treating PND in a preclinical application.

摘要

术后神经认知障碍(PND)最近被推荐用于定义围手术期的认知下降。然而,该疾病的潜在机制仍不清楚。微小 RNA(miRNA)是一种非编码 RNA,在调节神经再生和神经元凋亡方面发挥着重要作用。在这项研究中,心肺旁路(CPB)手术后 PND 大鼠模型中的 miR-124-3p 显著减少。构建了 miR-124-3p 过表达慢病毒,并通过 CPB 前的脑室内注射进行注射。 Morris 水迷宫测试(MWM)和旷场测试(OFT)用于测量行为变化,数据显示 CPB 后大鼠的认知功能下降。通过免疫组织化学(IHC)分析和酶联免疫吸附测定(ELISA),PND 大鼠表达更高的 Aβ和 p-Tau 蛋白。此外,IHC、ELISA、Western Blot 分析(WB)和末端脱氧核苷酸转移酶介导的缺口末端标记测定(TUNEL)的结果表明 CPB 程序在 PND 大鼠中诱导了炎症和细胞凋亡。数据还显示 miR-124-3p 过表达对 PND 的保护作用,可减轻炎症、细胞凋亡,并缓解修复后的认知功能。此外,miR-124-3p 通过直接靶向 LPIN1 进行预测。这项研究提供了一个新的观点,即 miR-124-3p 可以通过调节 LPIN1 改善 PND 的状态,从而为预防和治疗临床前应用中的 PND 提供了新策略。

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