Sirtuin 1 activation protects against early brain injury after experimental subarachnoid hemorrhage in rats.
Sirtuin 1 activation protects against early brain injury after experimental subarachnoid hemorrhage in rats.
复制标题
Sirtuin 1 激活可防止大鼠实验性蛛网膜下腔出血后的早期脑损伤。
DOI：
10.1038/cddis.2016.292
复制
发表时间：
2016-10-13
影响因子：
9
通讯作者：
Hang CH
中科院分区：
文献类型：
--
作者：
Zhang XS;Wu Q;Wu LY;Ye ZN;Jiang TW;Li W;Zhuang Z;Zhou ML;Zhang X;Hang CH
越来越多的证据表明，sirtuin 1（SIRT 1）与氧化应激、炎症和细胞凋亡等广泛的细胞功能有关。本研究旨在探讨SIRT 1在蛛网膜下腔出血（SAH）后脑组织中的变化及其在SAH早期脑损伤（EBI）中的作用。第一组实验中，将大鼠随机分为假手术组和SAH 2、6、12、24、48、72 h组。免疫印迹、免疫组化和免疫荧光检测SIRT 1的表达。在另一组实验中，利用SIRT 1特异性抑制剂（sirtinol）和激活剂（activator 3）来研究SIRT 1在SAH诱导的EBI中的作用。SIRT 1蛋白在SAH早期即明显升高，并于SAH后24 h达高峰。SIRT 1在神经元和小胶质细胞中均有表达，SAH后SIRT 1表达增强主要位于神经元。给予sirtinol抑制SAH后SIRT 1通路的表达和激活，而激活剂3增强SAH后SIRT 1通路的表达和激活。此外，SIRT 1的抑制可加重O类叉头转录因子、核因子-κ B和p53诱导的氧化损伤、神经炎症和神经元凋亡，导致SAH后脑损伤加重。相比之下，激活因子3治疗可以减少O类、核因子-κ B-和p53诱导的氧化损伤、神经炎症和神经元凋亡的叉头转录因子，以保护免受EBI。这些结果表明，SIRT 1通过去乙酰化和随后抑制O类、核因子-κ B和p53诱导的氧化、炎症和凋亡途径的叉头转录因子，在SAH后对EBI的神经保护中起重要作用。SIRT 1可能成为SAH治疗的新靶点。
Increasing evidence indicates that sirtuin 1 (SIRT1) is implicated in a wide range of cellular functions, such as oxidative stress, inflammation and apoptosis. The aim of this study was to investigate the change of SIRT1 in the brain after subarachnoid hemorrhage (SAH) and its role on SAH-induced early brain injury (EBI). In the first set of experiments, rats were randomly divided into sham group and SAH groups at 2, 6, 12, 24, 48 and 72 h. The expression of SIRT1 was evaluated by western blot analysis, immunohistochemistry and immunofluorescence. In another set of experiments, SIRT1-specific inhibitor (sirtinol) and activator (activator 3) were exploited to study the role of SIRT1 in SAH-induced EBI. It showed that the protein level of SIRT1 was markedly elevated at the early stage of SAH and peaked at 24 h after SAH. The expression of SIRT1 could be observed in neurons and microglia, and the enhanced SIRT1 was mainly located in neurons after SAH. Administration of sirtinol inhibited the expression and activation of SIRT1 pathways after SAH, while activator 3 enhanced the expression and activation of SIRT1 pathways after SAH. In addition, inhibition of SIRT1 could exacerbate forkhead transcription factors of the O class-, nuclear factor-kappa B- and p53-induced oxidative damage, neuroinflammation and neuronal apoptosis, leading to aggravated brain injury after SAH. In contrast, activator 3 treatment could reduce forkhead transcription factors of the O class-, nuclear factor-kappa B-, and p53-induced oxidative damage, neuroinflammation and neuronal apoptosis to protect against EBI. These results suggest that SIRT1 plays an important role in neuroprotection against EBI after SAH by deacetylation and subsequent inhibition of forkhead transcription factors of the O class-, nuclear factor-kappa B-, and p53-induced oxidative, inflammatory and apoptotic pathways. SIRT1 might be a new promising molecular target for SAH.
登录
查看更多内容
影响因子：
16.2
作者：
Herskovits AZ;Guarente L
通讯作者：
Guarente L
影响因子：
5.8
作者：
Chong ZZ;Shang YC;Wang S;Maiese K
通讯作者：
Maiese K
影响因子：
4.8
作者：
Cahill, Julian;Calvert, John W.;Zhang, John H.
通讯作者：
Zhang, John H.
影响因子：
3.6
作者：
Li, Zhiqing;Liang, Guobiao;Xue, Yixue
通讯作者：
Xue, Yixue
DOI：
10.1016/j.bbrc.2009.07.119
发表时间：
2009-10-02
影响因子：
3.1
作者：
Kakefuda, Kenichi;Fujita, Yasunori;Hara, Hideaki
通讯作者：
Hara, Hideaki