Stroke is one of the leading causes of mortality and disability worldwide. Long noncoding RNAs (lncRNAs) including MALAT1 have been shown to have critical roles in cerebral ischemia reperfusion injury (CIRI). However, the underlying mechanism of MALAT1 in CIRI has not been elucidated. The present study aimed to investigate the function and potential regulatory mechanism of MALAT1 in cerebral ischemic reperfusion injury. We established the middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation/reoxygenation (OGD/RX) model in vivo and in vitro, and then Cell Counting Kit-8 (CCK-8), RT-qPCR, flow cytometry analysis, lactate dehydrogenase (LDH) analysis, and 2,3,5-triphenyltetrazolium chloride (TTC) staining were used to examine cell viability, MALAT1, aquaporin-4 (AQP4) expression, LDH release, and infarct volume, respectively. The level of AQP4 was remarkably upregulated in CIRI 24 h/48 h or OGD/RX 24 h/48 h compared with the sham group. Knockdown of AQP4 could alleviate OGD/RX-induced injury through enhancing cell viability and reducing LDH release and the rate of apoptotic cells. Furthermore, we found that MALAT1 was also increased in OGD/RX 24 h/48 h and silencing of MALAT1 could decrease AQP4. Inhibition of MALAT1 could also protect OGD/RX-induced injury, while the protective effect of MALAT1 siRNA on cerebral ischemic reperfusion was disappeared after transfection with AQP4 plasmid, indicating that MALAT1 may play a protective role in brain stroke through regulating AQP4. Taken together, our study provides evidence that MALAT1 is involved in ischemic stroke by inhibiting AQP4. Therefore, MALAT1 may serve as a potential target for therapeutic intervention in ischemic brain injury.

中文翻译：

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抑制 LncRNA MALAT1 通过调节 AQP4 表达减轻脑缺血再灌注损伤

中风是世界范围内导致死亡和残疾的主要原因之一。包括 MALAT1 在内的长链非编码 RNA (lncRNA) 已被证明在脑缺血再灌注损伤 (CIRI) 中具有关键作用。然而，MALAT1 在 CIRI 中的潜在机制尚未阐明。本研究旨在探讨MALAT1在脑缺血再灌注损伤中的功能和潜在调控机制。我们在体内和体外建立大脑中动脉闭塞（MCAO）模型和氧-葡萄糖剥夺/复氧（OGD/RX）模型，然后细胞计数试剂盒-8（CCK-8）、RT-qPCR、流式细胞术分析、乳酸脱氢酶 (LDH) 分析和 2,3,5-三苯基氯化四唑 (TTC) 染色分别用于检查细胞活力、MALAT1、水通道蛋白 4 (AQP4) 表达、LDH 释放和梗塞体积。与假手术组相比，CIRI 24 h/48 h 或OGD/RX 24 h/48 h AQP4 水平显着上调。敲低 AQP4 可以通过增强细胞活力和减少 LDH 释放和凋亡细胞率来减轻 OGD/RX 诱导的损伤。此外，我们发现 MALAT1 在 OGD/RX 24 小时/48 小时中也增加，并且 MALAT1 的沉默可以降低 AQP4。抑制 MALAT1 也可以保护 OGD/RX 诱导的损伤，而 MALAT1 siRNA 对脑缺血再灌注的保护作用在转染 AQP4 质粒后消失，表明 MALAT1 可能通过调节 AQP4 在脑卒中发挥保护作用。总之，我们的研究提供了 MALAT1 通过抑制 AQP4 参与缺血性中风的证据。所以，