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热量限制可减轻 C57BL/6J 小鼠因真实环境颗粒物暴露引起的肺部损伤和肺外毒性。

Caloric restriction attenuates C57BL/6 J mouse lung injury and extra-pulmonary toxicity induced by real ambient particulate matter exposure.

机构信息

Department of Toxicology, School of Public Health, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou, 510080, China.

Department of Toxicology, School of Public Health, Qingdao University, Qingdao, 266021, China.

出版信息

Part Fibre Toxicol. 2020 Jun 5;17(1):22. doi: 10.1186/s12989-020-00354-2.

Abstract

BACKGROUND

Caloric restriction (CR) is known to improve health and extend lifespan in human beings. The effects of CR on adverse health outcomes in response to particulate matter (PM) exposure and the underlying mechanisms have yet to be defined.

RESULTS

Male C57BL/6 J mice were fed with a CR diet or ad libitum (AL) and exposed to PM for 4 weeks in a real-ambient PM exposure system located at Shijiazhuang, China, with a daily mean concentration (95.77 μg/m) of PM. Compared to AL-fed mice, CR-fed mice showed attenuated PM-induced pulmonary injury and extra-pulmonary toxicity characterized by reduction in oxidative stress, DNA damage and inflammation. RNA sequence analysis revealed that several pulmonary pathways that were involved in production of reactive oxygen species (ROS), cytokine production, and inflammatory cell activation were inactivated, while those mediating antioxidant generation and DNA repair were activated in CR-fed mice upon PM exposure. In addition, transcriptome analysis of murine livers revealed that CR led to induction of xenobiotic metabolism and detoxification pathways, corroborated by increased levels of urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) and decreased cytotoxicity measured in an ex vivo assay.

CONCLUSION

These novel results demonstrate, for the first time, that CR in mice confers resistance against pulmonary injuries and extra-pulmonary toxicity induced by PM exposure. CR led to activation of xenobiotic metabolism and enhanced detoxification of PM-bound chemicals. These findings provide evidence that dietary intervention may afford therapeutic means to reduce the health risk associated with PM exposure.

摘要

背景

热量限制(CR)已知可改善人类健康并延长寿命。CR 对颗粒物(PM)暴露引起的不良健康后果的影响及其潜在机制尚未确定。

结果

雄性 C57BL/6J 小鼠喂食 CR 饮食或自由进食(AL),并在中国石家庄的真实环境 PM 暴露系统中暴露于 PM 4 周,每日平均浓度(95.77μg/m)的 PM。与 AL 喂养的小鼠相比,CR 喂养的小鼠表现出 PM 诱导的肺损伤和肺外毒性减轻,其特征为氧化应激、DNA 损伤和炎症减少。RNA 序列分析显示,参与活性氧(ROS)产生、细胞因子产生和炎症细胞激活的几个肺途径失活,而在 PM 暴露时,介导抗氧化生成和 DNA 修复的途径在 CR 喂养的小鼠中被激活。此外,对小鼠肝脏的转录组分析表明,CR 导致外源代谢物和解毒途径的诱导,这与多环芳烃(PAHs)的尿液代谢物水平增加和体外测定的细胞毒性降低相符。

结论

这些新结果首次表明,CR 可使小鼠抵抗 PM 暴露引起的肺损伤和肺外毒性。CR 导致外源代谢物的激活和 PM 结合化学物质的解毒增强。这些发现为饮食干预可能提供治疗手段以降低与 PM 暴露相关的健康风险提供了证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4bf/7275546/d233437550fc/12989_2020_354_Fig1_HTML.jpg

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