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白藜芦醇对 PM2.5 诱导的小鼠肺氧化损伤的保护作用中自噬的调控。

Modulation of autophagy in the protective effect of resveratrol on PM2.5-induced pulmonary oxidative injury in mice.

机构信息

Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China.

Center for Disease Control and Prevention, Chengdu Railway Bureau, Chengdu, China.

出版信息

Phytother Res. 2018 Dec;32(12):2480-2486. doi: 10.1002/ptr.6187. Epub 2018 Sep 20.

Abstract

Ambient fine particulate matter (PM2.5) is capable of inducing pulmonary oxidative injury. Autophagy maintains basal cellular homeostasis and plays a critical role in the pathogenesis of lung diseases. Resveratrol, a natural polyphenol, is an effective antioxidant agent against particulate matter (PM)-induced injuries. The current study was designed to investigate whether resveratrol can regulate autophagy in the process of PM2.5-mediated pulmonary oxidative injury. In the mice model of PM2.5 exposure, we found that PM2.5 increased the contents of malondialdehyde (MDA) and nitric oxide (NO) while decreased the expression of nuclear factor erythroid-2-related factor 2 in the lungs. The levels of 8-hydroxydeoxyguanosine and inflammatory cytokines were increased following PM2.5 exposure. Histological analysis of the lungs revealed inflammatory change in PM2.5 group. Meanwhile, PM2.5 triggered autophagy, as evidenced by the elevated expression of microtubule-associated proteins light chain 3II, Beclin1 and p62. Transmission electron microscopy images showed that autophagosomes accumulated in the lungs after PM2.5 exposure. Furthermore, resveratrol intervention suppressed autophagy and attenuated the oxidative injury resulting from PM2.5 exposure. Our findings provided a valuable insight into the underlying mechanism for the protective effects of resveratrol against PM2.5-induced lung injury, which involves suppression of the autophagic process.

摘要

环境细颗粒物(PM2.5)能够诱导肺部氧化损伤。自噬维持细胞基础的内稳态,并在肺部疾病的发病机制中发挥关键作用。白藜芦醇是一种天然多酚,是一种有效的抗颗粒物质(PM)诱导损伤的抗氧化剂。本研究旨在探讨白藜芦醇是否能在 PM2.5 介导的肺部氧化损伤过程中调节自噬。在 PM2.5 暴露的小鼠模型中,我们发现 PM2.5 增加了丙二醛(MDA)和一氧化氮(NO)的含量,同时降低了肺部核因子红细胞 2 相关因子 2 的表达。8-羟基脱氧鸟苷和炎症细胞因子的水平在 PM2.5 暴露后增加。PM2.5 组肺部的组织学分析显示出炎症改变。同时,PM2.5 触发了自噬,这表现在微管相关蛋白轻链 3II、Beclin1 和 p62 的表达升高。透射电子显微镜图像显示,PM2.5 暴露后自噬体在肺部积累。此外,白藜芦醇干预抑制了自噬,并减轻了 PM2.5 暴露引起的氧化损伤。我们的研究结果为白藜芦醇对 PM2.5 诱导的肺损伤的保护作用的潜在机制提供了有价值的见解,即抑制自噬过程。

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