沉默长链非编码RNA HCG27通过调控miR-27a-3p改善缺血性中风后的认知功能障碍。

Silencing LncRNA HCG27 ameliorates cognitive dysfunction after ischemic stroke via miR-27a-3p regulation.

作者信息

Li Ting, Li Ying, Chen Lin, Zeng Chaosheng, Xing Huaijie, Chen Min, Yan Limin, Zhang Xiaopei

机构信息

Department of Neurology, The First People's Hospital of Shenyang, Shenyang, 110041, China.

The Tenth Sanatorium Department, Qingdao Special Service Sanatorium of PLA Navy, Qingdao, 266071, China.

出版信息

Hereditas. 2025 Jul 18;162(1):136. doi: 10.1186/s41065-025-00493-6.

DOI:10.1186/s41065-025-00493-6

PMID:40682202

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12275291/

Abstract

BACKGROUND

We explore the effect of improving cognitive dysfunction after cerebral ischemia-reperfusion (CI/R) by regulating HCG27.

METHODS

The MCAO and OGD/R methods were employed to establish in vivo and in vitro models of cognitive dysfunction caused by a CI/R injury. RT-qPCR was utilized to detect the relative expression of HCG27 and miR-27a-3p. An ELISA was adopted to measure the concentrations of inflammatory factors (IL-6, IL-1β, IL-10). The concentration of MDA and activity of CAT were detected using commercially available kits. The neurological deficit was evaluated using the mNSS score. The spatial learning and memory capabilities were evaluated via the MWM test. The targeting relationships were validated by the dual-luciferase reporter assay, RIP assay, and RNA pull-down assay. The CCK-8 assay and flow cytometry were employed to asses cell viability and apoptosis, respectively.

RESULTS

The level of HCG27 was upregulated in MCAO rats and OGD/R-induced BV2 cells, whereas that of miR-27a-3p decreased, and HCG27 targeted miR-27a-3p. Compared with the sham group, the mNSS score of MCAO rats was elevated, and their spatial learning and memory abilities declined, with aggravated inflammatory response and oxidative stress. However, silencing HCG27 improved these conditions, and the miR-27a-3p antagonist reversed this. MiR-27a-3p reversed the increase in cell viability in OGD/R-induced BV2 cells, reduced the cell apoptosis rate, and weakened the inflammatory response and oxidative stress caused by the HCG27 silencing.

CONCLUSIONS

Silencing HCG27 can protect against cognitive dysfunction after cerebrovascular disease by targeting miR-27a-3p.

摘要

背景

我们通过调节HCG27来探讨改善脑缺血再灌注（CI/R）后认知功能障碍的作用。

方法

采用大脑中动脉闭塞（MCAO）和氧糖剥夺/复氧（OGD/R）方法建立CI/R损伤所致认知功能障碍的体内和体外模型。运用逆转录定量聚合酶链反应（RT-qPCR）检测HCG27和miR-27a-3p的相对表达。采用酶联免疫吸附测定（ELISA）法检测炎症因子（IL-6、IL-1β、IL-10）的浓度。使用商业试剂盒检测丙二醛（MDA）浓度和过氧化氢酶（CAT）活性。采用改良神经功能缺损评分（mNSS）评估神经功能缺损。通过 Morris 水迷宫（MWM）试验评估空间学习和记忆能力。通过双荧光素酶报告基因检测、RNA 免疫沉淀（RIP）试验和 RNA 下拉试验验证靶向关系。分别采用细胞计数试剂盒-8（CCK-8）试验和流式细胞术评估细胞活力和凋亡。

结果

MCAO 大鼠和 OGD/R 诱导的 BV2 细胞中 HCG27 水平上调，而 miR-27a-3p 水平下降，且 HCG27 靶向 miR-27a-3p。与假手术组相比，MCAO 大鼠的 mNSS 评分升高，空间学习和记忆能力下降，炎症反应和氧化应激加重。然而，沉默 HCG27 可改善这些情况，而 miR-27a-3p 拮抗剂可逆转这一作用。miR-27a-3p 可逆转 OGD/R 诱导的 BV2 细胞活力增加，降低细胞凋亡率，并减弱 HCG27 沉默引起的炎症反应和氧化应激。