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血清微囊藻毒素-LR水平与炎症性肠病风险相关:中国一项配对病例对照研究

Serum Microcystin-LR Levels Linked with Risk of Inflammatory Bowel Disease: A Matched Case-Control Study in China.

作者信息

Chen Xuejie, Liu Wenya, Liao Yangjie, Xiang Xin, Yang Yue, Tian Li, Gao Xiang, Cao Qian, Guo Hong, Chao Kang, Song Fengmei, Liu Rongbei, Li Ying, Ye Shuyu, Wang Jiangang, Yang Fei, Wang Xiaoyan

机构信息

Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha, 410013, China.

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

出版信息

Environ Health (Wash). 2024 May 3;2(7):453-464. doi: 10.1021/envhealth.3c00212. eCollection 2024 Jul 19.

DOI:10.1021/envhealth.3c00212
PMID:39473886
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11503794/
Abstract

Microcystin-LR (MC-LR), the most prevalent and diverse cyanotoxin produced by harmful cyanobacterial blooms, has been linked to gastrointestinal toxicity. Therefore, we conducted a case-control study across four regions in China to investigate this relationship. Inflammatory bowel disease (IBD) cases (219) were matched with healthy controls (438) based on age and gender and conditional logistic regression models and Restricted cubic splines were used to evaluate the association between MC-LR exposure and IBD risk. We used quantitative real-time polymerase chain reaction to measure the expression levels of inflammatory factors. The levels of protein expression in the colorectum were determined using Western blotting (WB). Compared to the lowest quartile of serum MC-LR levels, the adjusted odds ratios and 95% confidence intervals (CI) for the highest quartiles of serum MC-LR levels were 5.51 (2.70, 11.21). The RCS was shown the association between serum MC-LR levels and IBD risk was nonlinear ( < 0.001). In the animal experiments, MC-LR resulted in colorectal injury via the PI3K/AKT signaling pathway. Our study provides the evidence that serum MC-LR exposure is significantly associated with the risk of IBD in China. Animal study results indicate that MC-LR probably causes IBD via the PI3K/AKT signaling pathway.

摘要

微囊藻毒素-LR(MC-LR)是有害蓝藻水华产生的最普遍、种类最多的蓝藻毒素,与胃肠道毒性有关。因此,我们在中国四个地区进行了一项病例对照研究,以调查这种关系。根据年龄和性别,将炎症性肠病(IBD)病例(219例)与健康对照(438例)进行匹配,并使用条件逻辑回归模型和受限立方样条来评估MC-LR暴露与IBD风险之间的关联。我们使用定量实时聚合酶链反应来测量炎症因子的表达水平。使用蛋白质印迹法(WB)测定结肠直肠中的蛋白质表达水平。与血清MC-LR水平最低四分位数相比,血清MC-LR水平最高四分位数的调整优势比和95%置信区间(CI)为5.51(2.70,11.21)。受限立方样条显示血清MC-LR水平与IBD风险之间的关联是非线性的(<0.001)。在动物实验中,MC-LR通过PI3K/AKT信号通路导致结肠直肠损伤。我们的研究提供了证据,表明在中国,血清MC-LR暴露与IBD风险显著相关。动物研究结果表明,MC-LR可能通过PI3K/AKT信号通路导致IBD。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2670/11503794/aa8b92c88aad/eh3c00212_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2670/11503794/4c4e34bb32bd/eh3c00212_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2670/11503794/18d88c33d9b8/eh3c00212_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2670/11503794/ef14e0ad90ce/eh3c00212_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2670/11503794/b4a7f1820e2f/eh3c00212_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2670/11503794/aa8b92c88aad/eh3c00212_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2670/11503794/4c4e34bb32bd/eh3c00212_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2670/11503794/18d88c33d9b8/eh3c00212_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2670/11503794/ef14e0ad90ce/eh3c00212_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2670/11503794/b4a7f1820e2f/eh3c00212_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2670/11503794/aa8b92c88aad/eh3c00212_0005.jpg

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本文引用的文献

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Alleviates the Colorectal Inflammation Induced by Low-Dose Sub-Chronic Microcystin-LR Exposure.减轻低剂量亚慢性微囊藻毒素-LR 暴露引起的结直肠炎症。
Toxins (Basel). 2023 Sep 19;15(9):579. doi: 10.3390/toxins15090579.
2
Evolving Trends and Burden of Inflammatory Bowel Disease in Asia, 1990-2019: A Comprehensive Analysis Based on the Global Burden of Disease Study.亚洲炎症性肠病的演变趋势和负担,1990-2019:基于全球疾病负担研究的综合分析。
J Epidemiol Glob Health. 2023 Dec;13(4):725-739. doi: 10.1007/s44197-023-00145-w. Epub 2023 Sep 1.
3
Microcystin-LR Induces and Aggravates Colitis through NLRP3 Inflammasome-Mediated Pyroptosis in Mice.
微囊藻毒素-LR 通过 NLRP3 炎性体介导的细胞焦亡诱导和加重小鼠结肠炎。
Toxins (Basel). 2023 Jul 6;15(7):447. doi: 10.3390/toxins15070447.
4
Biodegradation of MC-LR and its key bioactive moiety Adda by Sphingopyxis sp. YF1: Comprehensive elucidation of the mechanisms and pathways.鞘氨醇单胞菌属YF1对微囊藻毒素-LR及其关键生物活性部分Adda的生物降解:机制和途径的全面阐释
Water Res. 2023 Feb 1;229:119397. doi: 10.1016/j.watres.2022.119397. Epub 2022 Nov 20.
5
Microcystin-LR Combined with Cadmium Exposures and the Risk of Chronic Kidney Disease: A Case-Control Study in Central China.微囊藻毒素-LR 联合镉暴露与慢性肾脏病发病风险的病例对照研究:来自中国中部地区的一项研究
Environ Sci Technol. 2022 Nov 15;56(22):15818-15827. doi: 10.1021/acs.est.2c02287. Epub 2022 Oct 21.
6
Long-term environmental levels of microcystin-LR exposure induces colorectal chronic inflammation, fibrosis and barrier disruption via CSF1R/Rap1b signaling pathway.长期暴露于微囊藻毒素-LR 会通过 CSF1R/Rap1b 信号通路诱导结直肠慢性炎症、纤维化和屏障破坏。
J Hazard Mater. 2022 Oct 15;440:129793. doi: 10.1016/j.jhazmat.2022.129793. Epub 2022 Aug 18.
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Chronic exposure to low concentration of MC-LR caused hepatic lipid metabolism disorder.长期暴露于低浓度的 MC-LR 可导致肝脏脂质代谢紊乱。
Ecotoxicol Environ Saf. 2022 Jul 1;239:113649. doi: 10.1016/j.ecoenv.2022.113649. Epub 2022 May 20.
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Histological and chemical damage induced by microcystin-LR and microcystin-RR on land snail Helix aspersa tissues after acute exposure.微囊藻毒素-LR 和微囊藻毒素-RR 对急性暴露后陆地蜗牛 Helix aspersa 组织的组织学和化学损伤。
Comp Biochem Physiol C Toxicol Pharmacol. 2021 Jul;245:109031. doi: 10.1016/j.cbpc.2021.109031. Epub 2021 Mar 15.