期刊
EUROPEAN JOURNAL OF NEUROSCIENCE
卷 55, 期 7, 页码 1695-1708出版社
WILEY
DOI: 10.1111/ejn.15622
关键词
B-cell lymphoma 2; cerebral ischaemic injury; histone deacetylases 4; microRNA-203-3p; sevoflurane
资金
- Natural Science Foundation of Hubei Province [2016CFB441]
- National Natural Science Foundation of China [81870855]
This study demonstrates the neuroprotective effects of Sevoflurane in cerebral ischaemic injury. miR-203-3p enhances the protective effects of Sevo through up-regulation of Bcl-2 and down-regulation of HDAC4.
Sevoflurane (Sevo) is neuroprotective in ischaemic injury, but its specific mechanism in the disease from microRNA-203-3p/histone deacetylases 4/B-cell lymphoma 2 (miR-203-3p/HDAC4/Bcl-2) axis asks for a comprehensive explanation. A middle cerebral artery occlusion (MCAO) mouse model was established by nylon suture method. miR-203-3p and HDAC4 expression was measured in mouse brain tissues. The MCAO mice were exposed to Sevo or injected with miR-203-3p- or HDAC4-related plasmids. In response to Sevo treatment or plasmid interference, neurological function, brain pathology, neuronal apoptosis and inflammation were determined. The interactions of miR-203-3p and HDAC4, and HDAC4 and Bcl-2 were verified. MCAO mice presented down-regulated miR-203-3p and up-regulated HDAC4. Sevo improved neurological function, brain pathological damage and reduced neuronal apoptosis and inflammation in MCAO mice, while overexpressing miR-203-3p further enhanced those effects. HDAC4 overexpression antagonized the impacts of miR-203-3p up-regulation on MCAO mice. The targeting relation existed between miR-203-3p and HDAC4, as well as between HDAC4 and Bcl-2. It is clearly elucidated that miR-203-3p enhances the protective effects of Sevo on MCAO mice through elevating Bcl-2 and down-regulating HDAC4, potentially and clinically offering an effective treatment method with Sevo for cerebral ischaemic injury.
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