School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
Thromb Haemost. 2019 Mar;119(3):421-430. doi: 10.1055/s-0038-1676987. Epub 2019 Jan 7.
Inflammation plays an important role in thrombus formation, and Sirtuin 1 (SIRT1) negatively regulates inflammation via deacetylating nuclear factor-kappa B. However, the relationship between SIRT1-regulated inflammation and deep vein thrombosis (DVT) is still unknown.
The aim of this study was to investigate whether SIRT1 plays a critical role in inferior vena cava (IVC) stenosis-induced DVT.
Thrombus weight and histopathologic analysis of IVC were evaluated at different time points after IVC stenosis in rats. Serum levels of inflammatory cytokines and protein expressions of SIRT1, acetylated p65 (Ace-p65), phosphorylated p65 (p-p65) and tissue factor (TF) in thrombosed IVC were assessed. Besides, the effects of resveratrol (RES, a SIRT1 agonist) and EX527 (a selective SIRT1 inhibitor) on DVT were evaluated.
Thrombus weight was increased from 1 to 3 days after IVC stenosis, and then was decreased afterwards. Leukocytes infiltration appeared and serum levels of cytokines were significantly increased in rats of IVC stenosis. SIRT1 protein expression was significantly down-regulated at 1 hour and 1 day after stenosis, while p-p65, Ace-p65 and TF protein expressions appeared a contrary trend. RES reduced thrombus weight, leukocytes infiltration, levels of tumour necrosis factor-α and interleukin-1β and protein expressions of Ace-p65 and TF as well. Moreover, RES significantly increased the protein and messenger ribonucleic acid expressions of SIRT1, while EX527 abolished the protective effects of RES.
SIRT1 activation attenuated IVC stenosis-induced DVT via anti-inflammation in rats. Therefore, SIRT1 may be a potential therapeutic target that could ameliorate DVT.
炎症在血栓形成中发挥重要作用，Sirtuin 1（SIRT1）通过去乙酰化核因子-κB 负调控炎症。然而，SIRT1 调节的炎症与深静脉血栓形成（DVT）之间的关系仍不清楚。
本研究旨在探讨 SIRT1 是否在腔静脉狭窄引起的 DVT 中发挥关键作用。
在大鼠腔静脉狭窄后不同时间点评估血栓重量和腔静脉组织病理学分析。检测炎性细胞因子在血清中的水平和 SIRT1、乙酰化 p65（Ace-p65）、磷酸化 p65（p-p65）和组织因子（TF）在血栓形成的腔静脉中的蛋白表达。此外，还评估了白藜芦醇（RES，一种 SIRT1 激动剂）和 EX527（一种选择性 SIRT1 抑制剂）对 DVT 的影响。
腔静脉狭窄后 1 至 3 天血栓重量增加，然后减少。白细胞浸润出现，大鼠血清细胞因子水平明显升高。狭窄后 1 小时和 1 天 SIRT1 蛋白表达明显下调，而 p-p65、Ace-p65 和 TF 蛋白表达呈相反趋势。RES 减少了血栓重量、白细胞浸润、肿瘤坏死因子-α和白细胞介素-1β的水平以及 Ace-p65 和 TF 的蛋白表达。此外，RES 显著增加了 SIRT1 的蛋白和信使核糖核酸表达，而 EX527 则消除了 RES 的保护作用。
SIRT1 激活通过在大鼠体内抗炎减轻腔静脉狭窄引起的 DVT。因此，SIRT1 可能是改善 DVT 的潜在治疗靶点。
