百草枯通过激活 PI3K/AKT 信号通路增加 IL-6 的表达和氧化应激,从而破坏血脑屏障

IF 1.7 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL
Tao Liu, Fenshuang Zheng, Lin Liu, Hua Zhou, Tao Shen, Yanping Li, Wei Zhang
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引用次数: 0

摘要

背景百草枯(PQ)是一种常用的除草剂,急性或慢性接触后会产生神经毒性。虽然体外证据支持百草枯对多巴胺细胞的毒性,但其体内效应(尤其是慢性暴露)仍不明确。在本研究中,我们研究了慢性 PQ 暴露对血脑屏障(BBB)损伤的影响及其潜在机制。方法 以成年雄性 Sprague Dawley 大鼠和原代人脑微血管内皮细胞(PHBME)为动物和细胞模型,暴露于 PQ。采用伊文思蓝染色法和苏木精及伊红染色法检测 BBB 和脑组织损伤情况。通过酶联免疫吸附试验对炎症细胞因子进行定量分析。通过 Western 印迹检测 PI3K/AKT 信号通路的变化。结果 PQ 暴露可导致脑组织和 BBB 发生严重病变。在动物模型和细胞模型中,PQ暴露后IL-6和活性氧水平均显著上调。PQ能抑制PHBME细胞的增殖和迁移。PQ 处理可促进 PI3K 和 AKT 的磷酸化,而应用 PI3K 抑制剂可减轻 PQ 诱导的 IL-6 生成、氧化应激、BBB 破坏和脑组织损伤。结论 我们的研究表明,长期暴露于 PQ 会损害 BBB 功能并诱导脑组织损伤。PI3K/AKT 通路的过度激活、IL-6 生成的随之上调以及氧化应激的增加似乎是 PQ 暴露导致炎症损伤的介导因素。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Paraquat disrupts the blood–brain barrier by increasing IL-6 expression and oxidative stress through the activation of PI3K/AKT signaling pathway
Background Paraquat (PQ) is a frequently used herbicide with neurotoxic effects after acute or chronic exposure. Although in vitro evidence supports the PQ toxicity to dopamine cells, its in vivo effects (especially the chronic exposure) remain ambiguous. In this study, we investigated the effect of chronic PQ exposure on the blood–brain barrier (BBB) damage and the underlying mechanisms. Methods Adult male Sprague Dawley rats and primary human brain microvascular endothelial (PHBME) cells were exposed to PQ as the animal and cell models. Evans Blue staining and hematoxylin & eosin staining were conducted to examine the BBB and brain tissue damages. The inflammatory cytokines were quantified via enzyme linked immunosorbent assay. The changes of PI3K/AKT signaling pathway were detected by western blot. Results PQ exposure can cause significant pathological lesions in the brain tissues and the BBB. IL-6 and reactive oxygen species levels were found to be significantly upregulated after PQ exposure in both the animal and cell models. PQ treatment could arrest the cell proliferation and migration in PHBME cells. PQ treatment promoted the phosphorylation of PI3K and AKT, and the application of PI3K inhibitor could attenuate PQ-induced IL-6 production, oxidative stress, BBB disruption, and brain tissue damage. Conclusion Our study demonstrated that chronic PQ exposure could impair the BBB function and induce brain tissue damage. The overactivation of the PI3K/AKT pathway, consequent upregulation of IL-6 production, and increased oxidative stress appear to mediate the inflammatory damage resulting from PQ exposure.
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来源期刊
Open Medicine
Open Medicine Medicine-General Medicine
CiteScore
3.00
自引率
0.00%
发文量
153
审稿时长
20 weeks
期刊介绍: Open Medicine is an open access journal that provides users with free, instant, and continued access to all content worldwide. The primary goal of the journal has always been a focus on maintaining the high quality of its published content. Its mission is to facilitate the exchange of ideas between medical science researchers from different countries. Papers connected to all fields of medicine and public health are welcomed. Open Medicine accepts submissions of research articles, reviews, case reports, letters to editor and book reviews.
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