Restored microRNA-326-5p Inhibits Neuronal Apoptosis and Attenuates Mitochondrial Damage via Suppressing STAT3 in Cerebral Ischemia/Reperfusion Injury.
Restored microRNA-326-5p Inhibits Neuronal Apoptosis and Attenuates Mitochondrial Damage via Suppressing STAT3 in Cerebral Ischemia/Reperfusion Injury.
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DOI：
10.1186/s11671-021-03520-3
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发表时间：
2021-04-20
影响因子：
--
通讯作者：
Tang T
中科院分区：
文献类型：
--
作者：
Huang Y;Wang Y;Duan Z;Liang J;Xu Y;Zhang S;Tang T
研究极大地探索了microRNAs （miRNAs）在脑缺血/再灌注损伤（CI/RI）中的作用。但miR-326-5p在CI/RI中的具体机制尚不清楚。因此，本研究旨在揭示miR-326-5p/信号换能器和转录-3 （STAT3）轴在CI/RI中的作用机制。在体外和体内分别建立大鼠皮层神经元缺氧和葡萄糖剥夺（OGD）模型和Sprague-Dawley大鼠大脑中动脉闭塞（MCAO）模型模拟CI/RI。对ogd处理的神经元和MCAO大鼠进行功能丧失和功能获得测定。然后检测ogd处理的神经元的活力、凋亡、氧化应激和线粒体膜电位，以及MCAO大鼠脑组织的病理变化、凋亡和线粒体膜电位。检测ogd处理的MCAO大鼠神经元和脑组织中Mitofusin-2 （Mfn2）、miR-326-5p和STAT3的表达。在ogd处理的MCAO大鼠神经元和脑组织中，Mfn2和miR-326-5p降低，STAT3升高。miR-326-5p靶向并负调控STAT3的表达。恢复miR-326-5p或降低STAT3可增强ogd处理神经元的活力，抑制细胞凋亡和氧化应激，增加线粒体膜电位，增加Mfn2表达。上调miR-326-5p或下调STAT3可缓解MCAO大鼠脑组织病理改变，抑制细胞凋亡，上调线粒体膜电位和Mfn2表达。本研究阐明了上调miR-326-5p或下调STAT3通过提高Mfn2表达来预防CI/RI。
Studies have greatly explored the role of microRNAs (miRNAs) in cerebral ischemia/reperfusion injury (CI/RI). But the specific mechanism of miR-326-5p in CI/RI is still elusive. Hence, this study was to unmask the mechanism of miR-326-5p/signal transducer and activator of transcription-3 (STAT3) axis in CI/RI. Two models (oxygen and glucose deprivation [OGD] in primary rat cortical neurons and middle cerebral artery occlusion [MCAO] in Sprague–Dawley rats) were established to mimic CI/RI in vitro and in vivo, respectively. Loss- and gain-of function assays were performed with OGD-treated neurons and with MCAO rats. Afterward, viability, apoptosis, oxidative stress and mitochondrial membrane potential in OGD-treated neurons were tested, as well as pathological changes, apoptosis and mitochondrial membrane potential in brain tissues of MCAO rats. Mitofusin-2 (Mfn2), miR-326-5p and STAT3 expression in OGD-treated neurons and in brain tissues of MCAO rats were detected. Mfn2 and miR-326-5p were reduced, and STAT3 was elevated in OGD-treated neurons and brain tissues of MCAO rats. miR-326-5p targeted and negatively regulated STAT3 expression. Restoring miR-326-5p or reducing STAT3 reinforced viability, inhibited apoptosis and oxidative stress, increased mitochondrial membrane potential and increased Mfn2 expression in OGD-treated neurons. Up-regulating miR-326-5p or down-regulating STAT3 relieved pathological changes, inhibited apoptosis and elevated mitochondrial membrane potential and Mfn2 expression in brain tissues of rats with MCAO. This study elucidates that up-regulated miR-326-5p or down-regulated STAT3 protects against CI/RI by elevating Mfn2 expression.
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影响因子：
1.9
作者：
Athanasopoulos, Panagiotis;Mastoraki, Aikaterini;Arkadopoulos, Nikolaos
通讯作者：
Arkadopoulos, Nikolaos
影响因子：
3.9
作者：
Cai, Hua-An;Tao, Xi;Zhu, Yi-Min
通讯作者：
Zhu, Yi-Min
DOI：
10.1016/j.jstrokecerebrovasdis.2018.08.023
发表时间：
2019-01-01
影响因子：
2.5
作者：
Huang, Rong;Ma, Juan;Luan, Xinping
通讯作者：
Luan, Xinping
影响因子：
6.1
作者：
Wu WJ;Jiang CJ;Zhang ZY;Xu K;Li W
通讯作者：
Li W
影响因子：
2
作者：
Fu, Chuanyi;Chen, Shuijie;Zhao, Jiannong
通讯作者：
Zhao, Jiannong