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过表达 SIRT6 可以通过下调 NF-kB 减轻脑出血损伤。

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

机构信息

Department of Neurosurgery, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Street, Wuhan, 430060, China.

Department of Nephrology, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Street, Wuhan, 430060, China.

出版信息

Neuromolecular Med. 2023 Mar;25(1):53-63. doi: 10.1007/s12017-022-08715-0. Epub 2022 Jun 29.

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.

摘要

Sirtuin-6 (SIRT6),是 NAD(+)依赖的去乙酰化酶 sirtuins 家族的成员之一,已被证明对缺血性中风具有有益作用。然而,SIRT6 在脑出血 (ICH) 中的作用尚未有报道。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。我们随后发现,SIRT6 的过表达可减少脑损伤并增加 ICH 大鼠模型和血红素诱导的皮质神经元中的神经元存活。我们的进一步研究发现,SIRT6 的过表达可以通过下调 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 通过抑制 NF-kB 介导的炎症反应来抑制 NF-kB 的表达,在 ICH 中发挥神经保护作用。SIRT6 可能成为 ICH 的一个新的治疗靶点。

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