Dai Rouli, Li Wei, Han Bin
National Institute of Drug Clinical Trials, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Neurology, West China Longquan Hospital Sichuan University (The First People's Hospital of Longquanyi District Chengdu), Chengdu, China.
Neurol Res. 2025 Jul 10:1-14. doi: 10.1080/01616412.2025.2529569.
Cerebral ischemia-reperfusion (CI/R) injury is a significant hurdle in ischemic stroke treatment. Substantial evidence indicates that long non-coding RNAs (lncRNAs) are implicated in CI/R injury. Here, we explore the function of lncRNA MCM3AP-AS1 in CI/R injury.
Employed the middle cerebral artery occlusion/reperfusion (MCAO/R) mice model and oxygen-glucose deprivation/reoxygenation (OGD/R) HT22 cell model to mimic in vivo and in vitro CI/R injury. Morris water maze test assessed mice platform-finding latency and swimming distance. Real-time quantitative reverse transcription PCR were conducted to examine the levels of MCM3AP-AS1 and microRNA (miR)-27b-3p. Modified Neurological Severity Score (mNSS) assessed neurological deficits, and triphenyl tetrazolium chloride staining assessed cerebral infarct volume. Enzyme-linked immunosorbent assay quantified inflammatory factor levels. Cell count kit-8 and flow cytometry detected cell viability and apoptosis, respectively. Dual luciferase reporter and RNA immunoprecipitation assays verified targeting relationships.
MAMC3AP-AS1 expression decreased in the brain tissue of MCAO/R mice and OGD/R-treated cells, while miR-27b-3p levels were rose. Upregulating MCM3AP-AS1 notably suppressed mNSS scores, reduced infarct volume, and alleviated cognitive dysfunction in MCAO/R mice; however, miR-27b-3p attenuated the function of MCM3AP-AS1. Furthermore, OGD/R treatment inhibited cell viability, increased apoptosis, and promoted inflammatory factors secretion, MCM3AP-AS1 reversed these effects, but miR-27b-3p significantly impaired this reversal. Mechanistically, MCM3AP-AS1 targeted miR-27b-3p.
MCM3AP-AS1 exerts neuroprotection by attenuating miR-27b-3p levels, thereby mitigating CI/R injury.
脑缺血再灌注（CI/R）损伤是缺血性脑卒中治疗中的一个重大障碍。大量证据表明，长链非编码RNA（lncRNAs）与CI/R损伤有关。在此，我们探讨lncRNA MCM3AP-AS1在CI/R损伤中的作用。
采用大脑中动脉闭塞/再灌注（MCAO/R）小鼠模型和氧糖剥夺/复氧（OGD/R）HT22细胞模型来模拟体内和体外的CI/R损伤。Morris水迷宫试验评估小鼠找到平台的潜伏期和游泳距离。进行实时定量逆转录PCR以检测MCM3AP-AS1和微小RNA（miR）-27b-3p的水平。改良神经功能缺损评分（mNSS）评估神经功能缺损，氯化三苯基四氮唑染色评估脑梗死体积。酶联免疫吸附测定法定量炎症因子水平。细胞计数试剂盒-8和流式细胞术分别检测细胞活力和凋亡情况。双荧光素酶报告基因和RNA免疫沉淀试验验证靶向关系。
在MCAO/R小鼠的脑组织和OGD/R处理的细胞中，MAMC3AP-AS1表达降低，而miR-27b-3p水平升高。上调MCM3AP-AS1可显著抑制MCAO/R小鼠的mNSS评分，减小梗死体积，并减轻认知功能障碍；然而，miR-27b-3p减弱了MCM3AP-AS1的功能。此外，OGD/R处理抑制细胞活力，增加凋亡，并促进炎症因子分泌，MCM3AP-AS1可逆转这些作用，但miR-27b-3p显著削弱了这种逆转作用。机制上，MCM3AP-AS1靶向miR-27b-3p。
MCM3AP-AS1通过降低miR-27b-3p水平发挥神经保护作用，从而减轻CI/R损伤。
