尿毒症心肌病大鼠心脏组织对 PM2.5 诱导毒性的易感性增加与线粒体功能障碍水平升高有关。

IF 4.4 3区 医学 Q2 ENVIRONMENTAL SCIENCES
Bhavana Sivakumar, Gino A Kurian
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引用次数: 0

摘要

慢性肾脏病(CKD)患者经常会发生尿毒症性心肌病,其特点是线粒体功能障碍是其重要的病理介质之一。鉴于 PM2.5 特别针对心脏线粒体,会加剧毒性,本研究探讨了在 CKD 条件下 PM2.5 毒性严重程度的潜在变化。雌性 Wistar 大鼠每天暴露于浓度为 250 μg/m3 的 PM2.5 中 3 小时,持续 21 天,之后建立了腺嘌呤诱导的 CKD 模型。虽然暴露于PM2.5和诱导大鼠患CKD都会导致心肌病,但暴露于PM2.5的CKD动物的心肌肥厚和纤维化程度明显更严重。CKD+PM2.5动物的心电图记录显示ST段压低和QRS间期延长,PM2.5和CKD动物均显示ST段升高。亚细胞水平分析证实,CKD+ PM2.5 组的线粒体拷贝数明显偏低,线粒体生物能功能严重下降。与其他实验组相比,PGC1-α的显著下降进一步证实了CKD+ PM2.5动物线粒体功能的严重退化。此外,CKD+PM2.5动物的心肌钙化增强,增加了CKD动物对PM2.5毒性的易感性。总之,我们的研究结果表明,CKD 心肌对 PM2.5 诱导的毒性的易感性增加可能是由于严重的线粒体损伤和心肌钙化增加所致。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Increased Susceptibility of Cardiac Tissue to PM2.5-Induced Toxicity in Uremic Cardiomyopathic Rats Is Linked to Elevated Levels of Mitochondrial Dysfunction.

Patients with chronic kidney disease (CKD) frequently develop uremic cardiomyopathy, characterized by mitochondrial dysfunction as one of its pathologically significant mediators. Given that PM2.5 specifically targets cardiac mitochondria, exacerbating toxicity, this study addresses the potential alterations in the severity of PM2.5 toxicity in the context of CKD conditions. Female Wistar rats were exposed to PM2.5 at a concentration of 250 μg/m3 daily for 3 h for 21 days after which an adenine-induced CKD model was developed. While both PM2.5 exposure and the induction of CKD in rats lead to cardiomyopathy, the CKD animals exposed to PM2.5 exhibited a notably severe extent of myocardial hypertrophy and fibrosis. ECG recordings in CKD+ PM2.5 animals revealed a depressed ST segment and prolonged QRS interval, with both PM2.5 and CKD animals displaying an elevated ST segment. Subcellular level analysis confirmed a significantly low mitochondrial copy number and a severe decline in mitochondrial bioenergetic function in the CKD+ PM2.5 group. The prominent decline in PGC1-α further affirmed the severe mitochondrial functional deterioration in CKD+ PM2.5 animals compared to other experimental groups. Additionally, myocardial calcification was enhanced in CKD+ PM2.5 animals, heightening the susceptibility of CKD animals to PM2.5 toxicity. In summary, our findings suggest that the increased vulnerability of CKD myocardium to PM2.5-induced toxicity may be attributed to severe mitochondrial damage and increased calcification in the myocardium.

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来源期刊
Environmental Toxicology
Environmental Toxicology 环境科学-毒理学
CiteScore
7.10
自引率
8.90%
发文量
261
审稿时长
4.5 months
期刊介绍: The journal publishes in the areas of toxicity and toxicology of environmental pollutants in air, dust, sediment, soil and water, and natural toxins in the environment.Of particular interest are: Toxic or biologically disruptive impacts of anthropogenic chemicals such as pharmaceuticals, industrial organics, agricultural chemicals, and by-products such as chlorinated compounds from water disinfection and waste incineration; Natural toxins and their impacts; Biotransformation and metabolism of toxigenic compounds, food chains for toxin accumulation or biodegradation; Assays of toxicity, endocrine disruption, mutagenicity, carcinogenicity, ecosystem impact and health hazard; Environmental and public health risk assessment, environmental guidelines, environmental policy for toxicants.
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