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.

中文翻译：

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


慢性肾脏病 （CKD） 患者经常发展为尿毒症性心肌病，其特征是线粒体功能障碍是其具有病理意义的介质之一。鉴于 PM2.5 专门针对心脏线粒体，加剧了毒性，本研究解决了 CKD 情况下 PM2.5 毒性严重程度的潜在变化。雌性 Wistar 大鼠每天暴露于 250 μg/m3 浓度的 PM2.5 中 3 h，持续 21 d，之后开发腺嘌呤诱导的 CKD 模型。虽然大鼠 PM2.5 暴露和 CKD 诱导都会导致心肌病，但暴露于 PM2.5 的 CKD 动物表现出明显严重的心肌肥大和纤维化程度。CKD+ PM2.5 动物的心电图记录显示 ST 段降低和 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 组线粒体拷贝数显著降低，线粒体生物能量功能严重下降。PGC1-α 的显着下降进一步证实了与其他实验组相比，CKD+ PM2.5 动物的线粒体功能严重恶化。此外，CKD+ PM2.5 动物的心肌钙化增强，提高了 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归因于严重的线粒体损伤和心肌钙化增加。