Li Shengqin, Zhao Guangju, Chen Longwang, Ding Yinwei, Lian Jie, Hong Guangliang, Lu Zhongqiu
Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Mol Med Rep. 2016 Feb;13(2):1833-8. doi: 10.3892/mmr.2015.4710. Epub 2015 Dec 23.
Sirtuin 1 (SIRT1) acts via the deacetylation of a number of crucial transcription factors and has been implicated in various biological processes, including oxidative stress. Previous studies have indicated that nuclear factor, erythroid 2‑like 2 (NRF2) is an effective target of antioxidant therapy for paraquat (PQ) poisoning. However, the association between SIRT1 and NRF2 and their effects in PQ‑induced oxidative stress remains to be elucidated. The current study demonstrated that PQ exposure upregulated the expression of SIRT1 and NRF2 following 6‑ and 24‑h exposure in the lungs of mice. However, long‑term exposure to PQ significantly decreased the expression of SIRT1 and NRF2. Resveratrol is a SIRT1 activator, and strongly enhanced SIRT1 expression and attenuated the lung injury resulting from PQ exposure in the current study. Additionally, treatment with resveratrol upregulated the expression of NRF2 and glutathione, increased the activity of heme oxygenase‑1, superoxide dismutase and catalase, but depleted the expression of malondialdehyde. The present results demonstrated that resveratrol reduced PQ‑induced oxidative stress and lung injury, potentially through the positive feedback signaling loop between SIRT1 and NRF2.
沉默调节蛋白1(SIRT1)通过使多种关键转录因子去乙酰化发挥作用,并参与包括氧化应激在内的各种生物学过程。先前的研究表明,核因子红系2样2(NRF2)是百草枯(PQ)中毒抗氧化治疗的有效靶点。然而,SIRT1与NRF2之间的关联及其在PQ诱导的氧化应激中的作用仍有待阐明。当前研究表明,在小鼠肺部,PQ暴露6小时和24小时后上调了SIRT1和NRF2的表达。然而,长期暴露于PQ会显著降低SIRT1和NRF2的表达。白藜芦醇是一种SIRT1激活剂,在当前研究中强烈增强了SIRT1的表达,并减轻了PQ暴露导致的肺损伤。此外,白藜芦醇处理上调了NRF2和谷胱甘肽的表达,增加了血红素加氧酶-1、超氧化物歧化酶和过氧化氢酶的活性,但降低了丙二醛的表达。目前的结果表明,白藜芦醇可能通过SIRT1和NRF2之间的正反馈信号回路减轻PQ诱导的氧化应激和肺损伤。