Zhang Yin, Guan Ying, Dai Manni, Yang Yue, Yang Fei
Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
The First Affiliated Hospital of University of South China, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
J Toxicol Environ Health A. 2025 May 19;88(10):385-394. doi: 10.1080/15287394.2024.2443525. Epub 2025 Jan 8.
Microcystin-LR (MC-LR) a cyclic toxin produced by cyanobacterial species is known to exert detrimental effects on various organs, including lung. Several investigators demonstrated that MC-LR exerts pulmonary toxicity, but the underlying mechanisms remain unclear. This study aimed to investigate whether exposure to MC-LR-induced lung inflammation and examine the underlying mechanisms. Thirty specific pathogen-free (SPF) male mice were allocated into control and MC-LR treatment groups. Mice were intraperitoneally injected with physiological saline or MC-LR (20 μg/kg) daily for a total of 21 days. Our findings indicated that exposure to MC-LR-produced histopathological changes in lung tissue, including thickening of alveolar walls and inflammatory infiltration. MC-LR was found to upregulate mRNA expression levels of pro-inflammatory cytokines TNFα, IL-6, IL-1β, and IL-18. Further, MC-LR significantly elevated the expression levels of proteins associated with the NF-κB/NLRP3 pathway p-NF-κB, NLRP3, Caspase-1, ASC. The activation of NF-κB/NLRP3 pathway further promoted the release of inflammatory cytokine IL-1β and cleavage of pyroptosis-associated GSDMD protein. These findings indicate that MC-LR may induce lung inflammation by promoting cell pyroptosis via the activation of the NF-κB/NLRP3 pathway.
微囊藻毒素-LR（MC-LR）是一种由蓝藻产生的环状毒素，已知会对包括肺在内的各种器官产生有害影响。一些研究人员证明MC-LR具有肺毒性，但其潜在机制仍不清楚。本研究旨在调查暴露于MC-LR是否会引发肺部炎症并探究其潜在机制。将30只特定病原体-free（SPF）雄性小鼠分为对照组和MC-LR处理组。小鼠每天腹腔注射生理盐水或MC-LR（20μg/kg），共21天。我们的研究结果表明，暴露于MC-LR会导致肺组织出现组织病理学变化，包括肺泡壁增厚和炎症浸润。发现MC-LR会上调促炎细胞因子TNFα、IL-6、IL-1β和IL-18的mRNA表达水平。此外，MC-LR显著提高了与NF-κB/NLRP3通路相关的蛋白质p-NF-κB、NLRP3、Caspase-1、ASC的表达水平。NF-κB/NLRP3通路的激活进一步促进了炎性细胞因子IL-1β的释放和焦亡相关GSDMD蛋白的切割。这些发现表明，MC-LR可能通过激活NF-κB/NLRP3通路促进细胞焦亡来诱导肺部炎症。
