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聚苯乙烯微塑料对大鼠的心血管毒性:基于非靶向代谢组学分析

The cardiovascular toxicity of polystyrene microplastics in rats: based on untargeted metabolomics analysis.

作者信息

Song Zikai, Wu Haidi, Fang Xiaoqi, Feng Xuemin, Zhou Liting

机构信息

Department of Cardiology, The First Hospital of Jilin University, Changchun, China.

Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, China.

出版信息

Front Pharmacol. 2024 May 10;15:1336369. doi: 10.3389/fphar.2024.1336369. eCollection 2024.

Abstract

BACKGROUND

Polystyrene microplastics (PS-MPs) exhibit multi-target, multi-dimensional, chronic, and low toxicity to the cardiovascular system. They enter the bloodstream through the gastrointestinal tract and respiratory system, altering blood parameters and conditions, inducing thrombotic diseases, and damaging myocardial tissue through the promotion of oxidative stress and inflammatory responses in myocardial cells. However, many of the links and mechanisms remain unclear.

METHODS

In this study, 48 wistar rats were randomly divided into four groups and exposed to different concentrations of PS-MPs: control group (0 mg/kg/d), low dose group (0.5 mg/kg/d), middle dose group (5 mg/kg/d) and high dose group (50 mg/kg/d), with 12 rats in each group. After 90 consecutive days of intragastric administration of PS-MPs, biochemical markers in myocardium, aorta and blood were detected, and HE staining was performed to observe the toxic effects of PS-mps on cardiovascular system. Furthermore, non-targeted metabolomics methods were used to analyze the effect of PS-MPs exposure on the metabolism of cardiovascular system in rats, and to explore its potential molecular mechanism.

RESULTS

The results revealed no pathological changes in the heart and aorta following PS-MPs exposure. However, the myocardial enzyme levels in the high dose PS-MPs group of rats showed a significant increase. Moreover, exposure to polystyrene microplastics caused a disorder in lipid metabolism in rats, and led to an increase in indicators of inflammation and oxidative stress in myocardial and aortic tissues, but resulted in a decrease in the level of IL-6. Untargeted metabolomics results showed that metabolites with antioxidant and anti-inflammatory effects, including equol and 4-hydroxybenzoic acid, were significantly upregulated.

CONCLUSION

These results suggest that long-term exposure to high concentrations of PS-MPs may lead to abnormal lipid metabolism and cardiovascular system damage. The mechanism may be related to oxidative stress and inflammatory response. Exogenous antioxidants and changes in own metabolites may have a protective effect on the injury. Therefore, understanding the toxicological mechanism of PS-MPs not only helps to elucidate its pathogenesis, but also provides new ideas for the treatment of chronic diseases.

摘要

背景

聚苯乙烯微塑料(PS-MPs)对心血管系统具有多靶点、多维度、慢性和低毒性作用。它们通过胃肠道和呼吸系统进入血液循环,改变血液参数和状况,诱发血栓性疾病,并通过促进心肌细胞中的氧化应激和炎症反应来损害心肌组织。然而,许多联系和机制仍不清楚。

方法

在本研究中,48只Wistar大鼠被随机分为四组,并暴露于不同浓度的PS-MPs:对照组(0毫克/千克/天)、低剂量组(0.5毫克/千克/天)、中剂量组(5毫克/千克/天)和高剂量组(50毫克/千克/天),每组12只大鼠。连续90天经胃内给予PS-MPs后,检测心肌、主动脉和血液中的生化标志物,并进行苏木精-伊红(HE)染色以观察PS-MPs对心血管系统的毒性作用。此外,采用非靶向代谢组学方法分析PS-MPs暴露对大鼠心血管系统代谢的影响,并探索其潜在的分子机制。

结果

结果显示,PS-MPs暴露后心脏和主动脉未出现病理变化。然而,高剂量PS-MPs组大鼠的心肌酶水平显著升高。此外,暴露于聚苯乙烯微塑料会导致大鼠脂质代谢紊乱,并导致心肌和主动脉组织中的炎症和氧化应激指标升高,但导致白细胞介素-6水平降低。非靶向代谢组学结果表明,具有抗氧化和抗炎作用的代谢物,包括雌马酚和4-羟基苯甲酸,显著上调。

结论

这些结果表明,长期暴露于高浓度的PS-MPs可能导致脂质代谢异常和心血管系统损伤。其机制可能与氧化应激和炎症反应有关。外源性抗氧化剂和自身代谢物的变化可能对损伤具有保护作用。因此,了解PS-MPs的毒理学机制不仅有助于阐明其发病机制,还为慢性病的治疗提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a40/11127592/c766f71a90fe/fphar-15-1336369-g001.jpg

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