Histone deacetylase 6 interference protects mice against experimental stroke-induced brain injury via activating Nrf2/HO-1 pathway

被引:15
作者
Li, Jie [1 ]
Zhao, Yanping [1 ]
Shi, Junfeng [1 ]
Ren, Zhanyun [1 ]
Chen, Feng [1 ]
Tang, Wuzhuang [1 ]
机构
[1] Yangzhou Univ, Affiliated Yixing Clin Sch, Sch Med, Dept Neurol,Affiliated Yixing Hosp,Jiangsu Univ, 75 Tongzhenguan Rd,Yicheng St, Yixing 214200, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Histone deacetylase 6; Nrf2; HO-1; cerebral ischemia; reperfusion injury; oxidative stress; CEREBRAL-ARTERY OCCLUSION; CELLS;
D O I
10.1080/19768354.2019.1601132
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Cerebral stroke is a fatal disease with increasing incidence. The study was to investigate the role and mechanism of Histone deacetylase 6 (HDAC6) on experimental stroke-induced brain injury. The recombinant shRNA-HDAC6 or scramble shRNA lentivirus was transfected to ICR mice. Then, the ischemia/reperfusion injury (I/RI) mice were constructed using middle cerebral artery occlusion (MCAO) method. Brain TTC staining was used to determine infarct areas. Serum levels of oxidative stress-related factors were detected by enzyme linked immunosorbnent assay (ELISA). Realtime-qPCR (RT-qPCR) and Western blot were used to respectively detect mRNA and protein levels. HDAC6 was up-regulated in brain I/RI mice (MCAO group), and down-regulated again in MCAO mice transfected with shRNA-HDAC6 (MCAO + shRNA group). The infarct area of the MCAO mice was increased, neurological scores were higher, and serum protein levels of 3-NT, 4-HNE and 8-OHdG were higher. HDAC6 interference attenuated above effects. Though protein levels of Nrf2 and HO-1 in cytoplasm increased slightly in MCAO group, they increased significantly by HDAC6 interference. The protein levels of Nrf2 in cytoblast decreased significantly in MCAO group, and increased markedly by HDAC6 interference. HDAC6 interference protected mice against experimental stroke-induced brain injury via Nrf2/HO-1 pathway.
引用
收藏
页码:192 / 199
页数:8
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