The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People's Republic of China.
The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, People's Republic of China.
Sci Rep. 2020 Nov 12;10(1):19658. doi: 10.1038/s41598-020-71411-1.
Acute cerebral ischaemia may lead to serious consequences, including brain injury caused by uncontrolled reperfusion, which occurs when circulation is re-established. The long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) plays an important role in the immune system. However, the potential roles and underlying molecular mechanisms of NEAT1 in cerebral ischaemia/reperfusion (I/R) injury remain unclear. The aim of the present study was to investigate the function of the lncRNA NEAT1 in cerebral I/R injury and its potential beneficial effects on neurons. In our study, oxygen-glucose deprivation (OGD)/reoxygenation (OGD/R) was induced in vitro to mimic cerebral I/R injury. Cholecystokinin-octopeptide (CCK-8) was used to measure cell viability, and flow cytometry was used to measure cell apoptosis. Real-time quantitative PCR (qRT-PCR) was used to measure the expression of phenotypic markers of classically activated (M1) and alternatively activated (M2) microglia, and western blotting was performed to detect the levels of proteins related to the AKT/STAT3 pathway. The expression of the lncRNA NEAT1 was significantly upregulated in patients with ischaemic stroke, and knockdown of the lncRNA NEAT1 alleviated OGD/R-induced apoptosis and increased neuronal viability. Furthermore, the lncRNA NEAT1 may inhibit microglial polarization towards the M1 phenotype to reduce the damage caused by OGD/R and reduce the activity of the AKT/STAT3 pathway. In conclusion, the lncRNA NEAT1 may be a potential target for new therapeutic interventions for cerebral I/R.
急性脑缺血可导致严重后果，包括再灌注时不受控制的再灌注引起的脑损伤，再灌注是在循环重建时发生的。长链非编码 RNA（lncRNA）核富集丰富转录物 1（NEAT1）在免疫系统中发挥重要作用。然而，NEAT1 在脑缺血/再灌注（I/R）损伤中的潜在作用及其对神经元的潜在有益作用尚不清楚。本研究旨在探讨 lncRNA NEAT1 在脑 I/R 损伤中的作用及其对神经元的潜在有益作用。在我们的研究中，体外诱导氧葡萄糖剥夺（OGD）/再氧合（OGD/R）模拟脑 I/R 损伤。使用胆囊收缩素-octopeptide（CCK-8）测量细胞活力，使用流式细胞术测量细胞凋亡。实时定量 PCR（qRT-PCR）用于测量经典激活（M1）和替代激活（M2）小胶质细胞表型标志物的表达，Western blot 用于检测与 AKT/STAT3 通路相关的蛋白水平。缺血性脑卒中患者 lncRNA NEAT1 的表达明显上调，lncRNA NEAT1 的敲低减轻了 OGD/R 诱导的细胞凋亡并增加了神经元活力。此外，lncRNA NEAT1 可能抑制小胶质细胞向 M1 表型极化，从而减轻 OGD/R 引起的损伤并降低 AKT/STAT3 通路的活性。总之，lncRNA NEAT1 可能是脑 I/R 新治疗干预的潜在靶点。
