Overexpressing SIRT6 can Attenuate the Injury of Intracerebral Hemorrhage by Down-Regulating NF-kB.

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2023-03-01 Epub Date: 2022-06-29 DOI:10.1007/s12017-022-08715-0
Jing Cheng, Yan-Qin Fan, Wen-Fei Zhang, Guo Zhang, Kuo Zeng, Zhang Ye, Dan Zhao, Li-Quan Wu, Zhi-Biao Chen
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Abstract

Sirtuin-6 (SIRT6), a member of the sirtuins family of NAD ( +) dependent deacetylases, has been shown to have beneficial effects in ischemic stroke. However, the role of SIRT6 in intracerebral haemorrhage (ICH) has not reported. We observed that SIRT6 expression was down-regulated in human ICH patients and down-regulated in ICH-induced rat cortical neurons. We subsequently found that SIRT6 overexpression reduced brain tissue damage and increased neuronal survival in the ICH model of rats and hemin-induced cortical neurons. Our further study found that overexpression of SIRT6 can reduce inflammatory response by down-regulating the expression of NF-kB and thus promote the recovery of neurological function in ICH animals. In conclusion, SIRT6 can inhibit the expression of NF-kB and plays a neuroprotective role in ICH by inhibiting the NF-kB-mediated inflammatory response.SIRT6 could be a novel therapeutic target for ICH.

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过表达 SIRT6 可通过下调 NF-kB 减轻脑出血的损伤
Sirtuin 6(SIRT6)是依赖于 NAD ( +) 的去乙酰化酶 sirtuins 家族的成员,已被证明对缺血性中风有益处。然而,SIRT6 在脑内出血(ICH)中的作用尚未见报道。我们观察到 SIRT6 在人类 ICH 患者中表达下调,在 ICH 诱导的大鼠皮质神经元中表达下调。随后我们发现,在大鼠 ICH 模型和海明诱导的大脑皮层神经元中,SIRT6 的过表达可减少脑组织损伤,提高神经元存活率。我们的进一步研究发现,过表达 SIRT6 可通过下调 NF-kB 的表达来减轻炎症反应,从而促进 ICH 动物神经功能的恢复。总之,SIRT6 可抑制 NF-kB 的表达,并通过抑制 NF-kB 介导的炎症反应在 ICH 中发挥神经保护作用。
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4.30%
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567
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