<br>褪黑素抑制莠去津诱导的小鼠小脑线粒体损伤：调节 cGAS-STING-NLRP3 轴依赖性细胞焦亡,Science of the Total Environment

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褪黑素抑制莠去津诱导的小鼠小脑线粒体损伤：调节 cGAS-STING-NLRP3 轴依赖性细胞焦亡
Science of the Total Environment ( IF 8.2 ) Pub Date : 2023-11-28 , DOI: 10.1016/j.scitotenv.2023.168924
Lin Liu ₁ , Mu-Zi Li ₁ , Ming-Hui Yao ₁ , Tian-Ning Yang ₁ , Yi-Xi Tang ₁ , Jin-Long Li ₂

Affiliation

由于环境和生活方式的变化，神经系统疾病的全球患病率急剧增加。阿特拉津（ATZ）是一种难以降解的土壤和水污染物，具有众所周知的神经毒性。褪黑素 (MT) 是一种具有化学保护特性的抗氧化剂，对 ATZ 暴露引起的小脑损伤具有潜在的治疗作用。本研究的目的是探讨MT对ATZ暴露引起的小脑炎症反应和细胞焦亡的影响及其潜在机制。在这项研究中，C57BL/6J 小鼠接受 ATZ（170 毫克/公斤体重/天）和 MT（5 毫克/公斤体重/天）治疗 28 天。我们的结果表明，MT 减轻了 ATZ 暴露引起的小脑组织病理学变化、超微结构损伤、氧化应激和线粒体膜电位 (ΔΨm) 降低。 ATZ暴露损伤线粒体导致线粒体DNA（mtDNA）释放到细胞质，MT激活环GMP-AMP合成酶干扰素基因刺激器（cGAS-STING）轴以减轻ATZ暴露引起的炎症和细胞焦亡。总的来说，我们的研究提供了新的证据，表明 cGAS-STING-NLRP3 轴在 MT 治疗 ATZ 诱导的小脑损伤中发挥着重要作用。

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Melatonin inhibits atrazine-induced mitochondrial impairment in cerebellum of mice: Modulation of cGAS-STING-NLRP3 axis-dependent cell pyroptosis

The global prevalence of Neurological disorders has increased alarmingly in response to environmental and lifestyle changes. Atrazine (ATZ) is a difficult to degrade soil and water pollutant with well-known neurotoxicity. Melatonin (MT), an antioxidant with chemoprotective properties, has a potential therapeutic effect on cerebellar damage caused by ATZ exposure. The aim of this study was to explore the effects and underlying mechanisms of MT on the cerebellar inflammatory response and pyroptosis induced by ATZ exposure. In this study, C57BL/6J mice were treated with ATZ (170 mg/kg BW/day) and MT (5 mg/kg BW/day) for 28 days. Our results revealed that MT alleviated the histopathological changes, ultrastructural damage, oxidative stress and decrease of mitochondrial membrane potential (ΔΨm) in the cerebellum induced by ATZ exposure. ATZ exposure damaged the mitochondria leading to release of mitochondrial DNA (mtDNA) to the cytoplasm, MT activated the cyclic GMP-AMP synthetase interferon gene stimulator (cGAS-STING) axis to alleviate inflammation and pyroptosis caused by ATZ exposure. In general, our study provided new evidence that the cGAS-STING-NLRP3 axis plays an important role in the treatment of ATZ-induced cerebellar injury by MT.

更新日期：2023-11-28

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