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上调微小RNA-214-3p通过抑制硫氧还蛋白相互作用蛋白(TXNIP)的表达减轻缺氧缺血性脑损伤。

Up-regulating microRNA-214-3p relieves hypoxic-ischemic brain damage through inhibiting TXNIP expression.

作者信息

Zhang Miaoyu, Zhou Haiyang, He Rongni, Yang Juan, Zou Yang, Deng Yiting, Xie Huifang, Yan Zhenxing

机构信息

Department of Neurology, The Second Clinical College of Southern Medical University, Guangzhou, 510280, Guangdong, China.

Department of Neurology, Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, 511518, Guangdong, China.

出版信息

Mol Cell Biochem. 2023 Mar;478(3):597-608. doi: 10.1007/s11010-022-04530-0. Epub 2022 Aug 18.

Abstract

A list of microRNAs (miRs) has been referred to involve in the development of hypoxic-ischemic brain damage (HIBD). Based on that, we probed the concrete role of miR-214-3p regulating thioredoxin-interacting protein (TXNIP) in the illness. A neonatal HIBD mouse model was established using the Rice-Vannucci method, followed by measurements of miR-214-3p and TXNIP levels in brain tissues. After modeling, mice were given brain injection of the compounds that could alter miR-214-3p and TXNIP expression. Afterward, neurological function, neuronal inflammation, neuronal apoptosis, neuron morphology, and the number of Nissl body were assessed in HIBD mice. The binding of miR-214-3p to TXNIP was analyzed. Lower miR-214-3p and higher TXNIP were analyzed in brain tissues of mice with HIBD. Up-regulating miR-214-3p or depleting TXNIP improved neurological function, reduced neuronal inflammation and neuronal apoptosis, attenuated morphological damage of neurons, and increased the number of Nissl bodies in mice with HIBD. TXNIP was targeted by miR-214-3p and overexpressing TXNIP reversed the therapeutic effect of miR-214-3p on HIBD mice. It is noted that promotion of miR-214-3p relieves HIBD in mice through inhibiting TXNIP expression.

摘要

已有一份微小RNA(miR)清单被提及与缺氧缺血性脑损伤(HIBD)的发生发展有关。基于此,我们探究了miR-214-3p调控硫氧还蛋白相互作用蛋白(TXNIP)在该疾病中的具体作用。采用Rice-Vannucci方法建立新生小鼠HIBD模型,随后检测脑组织中miR-214-3p和TXNIP水平。建模后,给小鼠脑内注射可改变miR-214-3p和TXNIP表达的化合物。之后,对HIBD小鼠的神经功能、神经元炎症、神经元凋亡、神经元形态及尼氏体数量进行评估。分析miR-214-3p与TXNIP的结合情况。HIBD小鼠脑组织中miR-214-3p水平降低而TXNIP水平升高。上调miR-214-3p或降低TXNIP可改善HIBD小鼠的神经功能,减少神经元炎症和神经元凋亡,减轻神经元形态损伤,并增加尼氏体数量。TXNIP是miR-214-3p的靶标,过表达TXNIP可逆转miR-214-3p对HIBD小鼠的治疗作用。值得注意的是,促进miR-214-3p表达可通过抑制TXNIP表达减轻小鼠的HIBD。

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