PM 暴露通过激活 NLRP3 介导体细胞炎症反应促进急性肾损伤的进展。
PM exposure promotes the progression of acute kidney injury by activating NLRP3-mediated macrophage inflammatory response.
机构信息
College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China.
Reproductive medical center, Department of Obstetrics and Gynecology, The Second Norman Bethune Hospital Of Jilin University, Changchun Jilin, 130000, China.
出版信息
Ecotoxicol Environ Saf. 2024 Jun 15;278:116454. doi: 10.1016/j.ecoenv.2024.116454. Epub 2024 May 14.
AIM
We reveal the mechanism of action whereby ambient PM promotes kidney injury.
METHODS
Using C57BL/6 mice, the effects of PM exposure on the acute kidney injury (AKI) were investigated, including renal function changes, expression of inflammatory cytokines, histopathological changes, as well as activation of nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3（NLRP3）. The effects of PM on renal injury after NLRP3 inhibition were explored using NLRP3 inhibitor (MCC950) and NLRP3 knockout mice. The effects of PM on the inflammatory response of renal macrophages were investigated at the cellular level.
RESULTS
PM exposure could promote kidney injury, NLRP3 activation and inflammatory response in mice. After using MCC950 and NLRP3 knockout mice, the effects of PM and the kidney injury could be inhibited. The cellular-level results also suggested that MCC950 could inhibit the effects of PM.
CONCLUSION
PM can promote the progression of AKI and aggravate tissue inflammation through NLRP3, which is an important environmental toxicological mechanism of PM.
目的
揭示环境 PM 促进肾脏损伤的作用机制。
方法
采用 C57BL/6 小鼠，研究 PM 暴露对急性肾损伤（AKI）的影响，包括肾功能变化、炎症细胞因子表达、组织病理学变化以及核苷酸结合寡聚结构域、富含亮氨酸重复和吡咯烷结构域包含蛋白 3（NLRP3）的激活。使用 NLRP3 抑制剂（MCC950）和 NLRP3 敲除小鼠，探讨 PM 对 NLRP3 抑制后肾损伤的影响。在细胞水平上研究 PM 对肾脏巨噬细胞炎症反应的影响。
结果
PM 暴露可促进小鼠肾脏损伤、NLRP3 激活和炎症反应。使用 MCC950 和 NLRP3 敲除小鼠后，PM 的作用和肾脏损伤均可被抑制。细胞水平的结果也表明 MCC950 可以抑制 PM 的作用。
结论
PM 可通过 NLRP3 促进 AKI 的进展并加重组织炎症，这是 PM 的一个重要环境毒理学机制。
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