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减轻低剂量亚慢性微囊藻毒素-LR 暴露引起的结直肠炎症。

Alleviates the Colorectal Inflammation Induced by Low-Dose Sub-Chronic Microcystin-LR Exposure.

机构信息

The Key Laboratory of Typical Environmental Pollution and Health Hazards of Hunan Province, Department of Epidemiology and Health Statistics, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China.

Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha 410017, China.

出版信息

Toxins (Basel). 2023 Sep 19;15(9):579. doi: 10.3390/toxins15090579.

Abstract

Microcystin-LR (MC-LR) contamination is a worldwide environmental problem that poses a grave threat to the water ecosystem and public health. Exposure to MC-LR has been associated with the development of intestinal injury, but there are no effective treatments for MC-LR-induced intestinal disease. Probiotics are "live microorganisms that are beneficial to the health of the host when administered in sufficient quantities". It has been demonstrated that probiotics can prevent or treat a variety of human diseases; however, their ability to mitigate MC-LR-induced intestinal harm has not yet been investigated. The objective of this study was to determine whether probiotics can mitigate MC-LR-induced intestinal toxicity and its underlying mechanisms. We first evaluated the pathological changes in colorectal tissues using an animal model with sub-chronic exposure to low-dose MC-LR, HE staining to assess colorectal histopathologic changes, qPCR to detect the expression levels of inflammatory factors in colorectal tissues, and WB to detect the alterations on CSF1R signaling pathway proteins in colorectal tissues. Microbial sequencing analysis and screening of fecal microorganisms differential to MC-LR treatment in mice. To investigate the role of microorganisms in MC-LR-induced colorectal injury, an in vitro model of MC-LR co-treatment with microorganisms was developed. Our findings demonstrated that MC-LR treatment induced an inflammatory response in mouse colorectal tissues, promoted the expression of inflammatory factors, activated the CSF1R signaling pathway, and significantly decreased the abundance of . In a model of co-treatment with MC-LR and (), it was discovered that substantially reduced the incidence of the colorectal inflammatory response induced by MC-LR and inhibited the protein expression of the CSF1R signaling pathway. This is the first study to suggest that inhibits the CSF1R signaling pathway to reduce the incidence of MC-LR-induced colorectal inflammation. This research may provide an excellent experimental foundation for the development of strategies for the prevention and treatment of intestinal diseases in MC-LR.

摘要

微囊藻毒素-LR(MC-LR)污染是一个全球性的环境问题,对水生态系统和公众健康构成严重威胁。暴露于 MC-LR 与肠道损伤的发展有关,但目前尚无针对 MC-LR 诱导的肠道疾病的有效治疗方法。益生菌是“当以足够的量施用时对宿主健康有益的活微生物”。已经证明益生菌可以预防或治疗多种人类疾病;然而,它们减轻 MC-LR 诱导的肠道损伤的能力尚未得到研究。本研究旨在确定益生菌是否可以减轻 MC-LR 诱导的肠道毒性及其潜在机制。我们首先使用亚慢性低剂量 MC-LR 暴露的动物模型评估结直肠组织的病理变化,使用 HE 染色评估结直肠组织的组织病理学变化,使用 qPCR 检测结直肠组织中炎症因子的表达水平,以及使用 WB 检测结直肠组织中 CSF1R 信号通路蛋白的变化。微生物测序分析和筛选 MC-LR 处理小鼠粪便中的差异微生物。为了研究微生物在 MC-LR 诱导的结直肠损伤中的作用,我们建立了 MC-LR 与微生物共同处理的体外模型。我们的研究结果表明,MC-LR 处理诱导了小鼠结直肠组织的炎症反应,促进了炎症因子的表达,激活了 CSF1R 信号通路,并显著降低了 的丰度。在 MC-LR 和 ()共同处理的模型中,发现 显著降低了 MC-LR 诱导的结直肠炎症反应的发生率,并抑制了 CSF1R 信号通路的蛋白表达。这是第一项表明 抑制 CSF1R 信号通路以减少 MC-LR 诱导的结直肠炎症发生率的研究。这项研究可能为开发 MC-LR 相关肠道疾病的预防和治疗策略提供极好的实验基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d5/10536654/7a37dfb4ca78/toxins-15-00579-g001.jpg

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