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正电子发射断层显像/X线计算机体层成像(PET/CT)用于检测和定位三甲基氯化锡所致神经系统损伤的可行性研究

Feasibility study of PET/CT for the detection and localization of nervous system damage caused by trimethyltin chloride.

作者信息

Liu Anqing, Tu Qingqiang, Huang Ming

机构信息

School of Public Health, Southern Medical University, Guangzhou, China.

Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou, China.

出版信息

Sci Rep. 2025 Jan 8;15(1):1353. doi: 10.1038/s41598-024-82473-w.

DOI:10.1038/s41598-024-82473-w
PMID:39779731
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11711231/
Abstract

Trimethyltin chloride (TMT), an organotin compound with potent neurotoxicity, is widely used as a heat stabilizer for plastics. However, the precise pathogenic mechanism of TMT remains incompletely elucidated, and there persists a dearth of sensitive detection methodologies for early diagnosis of TMT. In this study, Sprague-Dawley rats were treated with 10 mg/kg TMT to simulate acute exposure in humans. Micro-positron emission tomography/computed tomography (Micro-PET/CT) and molecular imaging quantitative analysis tools were employed to calculate the uptake rate of 18 F-2-fluoro-D-deoxy-glucose in each functional region of brain tissue. At the same time, the neurobehavioral test and neuropathological results of the experimental rats were compared, aiming to assess the feasibility of PET/CT in the detection and localization of TMT nervous system damage from many aspects. The results showed that TMT decreased glucose uptake in a wide range of brain tissues in rats, and impaired the memory, muscle strength, coordination ability and emotion of rats. Moreover, TMT induced neuronal damage within the cerebral cortex, hippocampal CA1, CA3 and DG regions as well as the cerebellum while also promoting gliosis surrounding the hippocampus. PET/CT imaging results are highly consistent with behavioral and pathological results. In conclusion, TMT induces a widespread reduction in energy metabolism across various brain regions, and PET/CT can serve as a sensitive detection method for TMT-induced encephalopathy.

摘要

三甲基氯化锡(TMT)是一种具有强大神经毒性的有机锡化合物,被广泛用作塑料的热稳定剂。然而,TMT的确切致病机制仍未完全阐明,并且仍然缺乏用于TMT早期诊断的灵敏检测方法。在本研究中,用10毫克/千克的TMT处理Sprague-Dawley大鼠,以模拟人类的急性暴露情况。采用微型正电子发射断层扫描/计算机断层扫描(Micro-PET/CT)和分子成像定量分析工具来计算脑组织各功能区域中18F-2-氟-D-脱氧葡萄糖的摄取率。同时,比较实验大鼠的神经行为测试和神经病理学结果,旨在从多个方面评估PET/CT在检测和定位TMT神经系统损伤方面的可行性。结果表明,TMT降低了大鼠广泛脑组织中的葡萄糖摄取,并损害了大鼠的记忆力、肌肉力量、协调能力和情绪。此外,TMT诱导大脑皮质、海马CA1、CA3和DG区域以及小脑中的神经元损伤,同时还促进海马周围的胶质细胞增生。PET/CT成像结果与行为和病理结果高度一致。总之,TMT诱导各个脑区的能量代谢广泛降低,并且PET/CT可作为TMT诱导性脑病的灵敏检测方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0603/11711231/bcd08add41ef/41598_2024_82473_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0603/11711231/86dc3d5669ae/41598_2024_82473_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0603/11711231/bcd08add41ef/41598_2024_82473_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0603/11711231/86dc3d5669ae/41598_2024_82473_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0603/11711231/11832a996fdd/41598_2024_82473_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0603/11711231/f586ac85df20/41598_2024_82473_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0603/11711231/3d6e1170ba8d/41598_2024_82473_Fig4_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0603/11711231/bcd08add41ef/41598_2024_82473_Fig6_HTML.jpg

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本文引用的文献

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[Three cases of occupational acute trimethyltin chloride poisoning].[三例职业性急性氯化三甲基锡中毒]
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2023 Jul 20;41(7):546-549. doi: 10.3760/cma.j.cn121094-20220414-00195.
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Pharmacological Modulation of Excitotoxicity through the Combined Use of NMDA Receptor Inhibition and Group III mGlu Activation Reduces TMT-Induced Neurodegeneration in the Rat Hippocampus.通过联合使用 NMDA 受体抑制和 mGluR3 激活对兴奋性毒性进行药理学调节可减少 TMT 诱导的大鼠海马神经元变性。
Int J Mol Sci. 2023 May 4;24(9):8249. doi: 10.3390/ijms24098249.
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Positron emission tomography: Evolving modalities, radiopharmaceuticals and professional collaboration.
正电子发射断层扫描:不断发展的模式、放射性药物和专业协作。
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[Follow up analysis of 6 patients with severe trimethyltin chloride poisoning for 4 years].6例重度氯化三甲基锡中毒患者4年随访分析
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The effect of URB597, exercise or their combination on the performance of 6-OHDA mouse model of Parkinson disease in the elevated plus maze, tail suspension test and step-down task.URB597、运动及其联合对帕金森病 6-OHDA 小鼠模型在高架十字迷宫、悬尾试验和跳台任务中表现的影响。
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The main mechanisms of trimethyltin chloride-induced neurotoxicity: Energy metabolism disorder and peroxidation damage.三甲基氯化锡致神经毒性的主要机制:能量代谢紊乱和过氧化损伤。
Toxicol Lett. 2021 Jul 1;345:67-76. doi: 10.1016/j.toxlet.2021.04.008. Epub 2021 Apr 15.
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Acute Trimethyltin Poisoning Caused by Exposure to Polyvinyl Chloride Production: 8 Cases.急性三甲基锡中毒由接触聚氯乙烯生产引起:8 例报告。
Am J Med Sci. 2021 Jul;362(1):92-98. doi: 10.1016/j.amjms.2021.02.010. Epub 2021 Feb 13.
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