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IL-10 通过激活 AMPK/SIRT1/PGC-1α 通路减轻 PM2.5 诱导的肺损伤。

IL-10 ameliorates PM2.5-induced lung injury by activating the AMPK/SIRT1/PGC-1α pathway.

机构信息

Department of Respiratory Medicine, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, Hebei, China; Department of Gerontology, Hebei General Hospital, Shijiazhuang, 050051, Hebei, China.

Department of Gerontology, Hebei General Hospital, Shijiazhuang, 050051, Hebei, China.

出版信息

Environ Toxicol Pharmacol. 2021 Aug;86:103659. doi: 10.1016/j.etap.2021.103659. Epub 2021 Apr 16.

DOI:10.1016/j.etap.2021.103659
PMID:33862202
Abstract

Exposure to fine particulate matter with a diameter ≤2.5 μm (PM2.5) can cause a number of respiratory diseases. However, there is currently no safe treatment for PM2.5-induced lung damage. This study investigated the protective effect of IL-10 against lung injury and the possible involvement of AMPK/SIRT1/PGC-1α signaling. The mean diameter, particle size distribution, and zeta potential of PM2.5 samples were assessed using a Zetasizer Nano ZS90 analyzer. Thereafter, Wistar rats were exposed to PM2.5 (1.8, 5.4, or 16.2 mg/kg) alone or high-dose PM2.5 with recombinant rat IL-10 (rrIL-10; 5 μg/rat). Treatment with rrIL-10 ameliorated PM2.5-induced acute lung injury, reduced mitochondrial damage, and inhibited inflammation, oxidative stress, and apoptosis in the PM2.5-treated rats. Moreover, the mRNA and protein expression of AMPK, SIRT1, and PGC-1α were upregulated by rrIL-10 treatment. In conclusion, rrIL-10 protected lung tissues against PM2.5-induced inflammation by reducing oxidative stress and apoptosis via activating AMPK/SIRT1/PGC-1α signaling.

摘要

暴露于直径≤2.5μm 的细颗粒物(PM2.5)可引起多种呼吸道疾病。然而,目前针对 PM2.5 引起的肺损伤尚无安全的治疗方法。本研究探讨了 IL-10 对肺损伤的保护作用及其可能涉及的 AMPK/SIRT1/PGC-1α信号通路。使用 Zetasizer Nano ZS90 分析仪评估 PM2.5 样品的平均直径、粒度分布和 ζ 电位。此后,Wistar 大鼠单独暴露于 PM2.5(1.8、5.4 或 16.2mg/kg)或高剂量 PM2.5 与重组大鼠 IL-10(rrIL-10;5μg/大鼠)。rrIL-10 治疗可改善 PM2.5 诱导的急性肺损伤,减轻线粒体损伤,并抑制 PM2.5 处理大鼠的炎症、氧化应激和细胞凋亡。此外,rrIL-10 治疗可上调 AMPK、SIRT1 和 PGC-1α 的 mRNA 和蛋白表达。总之,rrIL-10 通过激活 AMPK/SIRT1/PGC-1α 信号通路减轻氧化应激和细胞凋亡,从而保护肺组织免受 PM2.5 诱导的炎症。

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