铁死亡在 Dahl 盐敏感型高血压大鼠心脏和肾脏组织纤维化中的作用

The Participation of Ferroptosis in Fibrosis of the Heart and Kidney Tissues in Dahl Salt-Sensitive Hypertensive Rats.

作者信息

Huang Ya-Qi, Peng Kuang, Yan Jun, Chen Hui-Lin, Jiang Pei-Yong, Du Ya-Fang, Ling Xiang, Zhang Si-Liang, Wu Jie

机构信息

Department of Cardiology, The First Affiliated Hospital of University of South China, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, PR China.

出版信息

Am J Hypertens. 2024 Sep 16;37(10):784-791. doi: 10.1093/ajh/hpae076.

DOI:10.1093/ajh/hpae076

PMID:38850192

Abstract

BACKGROUND

Salt-sensitive hypertension is often more prone to induce damage to target organs such as the heart and kidneys. Abundant recent studies have demonstrated a close association between ferroptosis and cardiovascular diseases. Therefore, we hypothesize that ferroptosis may be closely associated with organ damage in salt-sensitive hypertension. This study aimed to investigate whether ferroptosis is involved in the occurrence and development of myocardial fibrosis and renal fibrosis in salt-sensitive hypertensive rats.

METHODS

Ten 7-week-old male Dahl salt-sensitive (Dahl-SS) rats were adaptively fed for 1 week, then randomly divided into two groups and fed either a normal diet (0.3% NaCl, normal diet group) or a high-salt diet (8% NaCl, high-salt diet group) for 8 weeks. Blood pressure of the rats was observed, and analysis of the hearts and kidneys of Dahl-SS rats was conducted via hematoxylin-eosin (HE) staining, Masson staining, Prussian blue staining, transmission electron microscopy, tissue iron content detection, malondialdehyde content detection, immunofluorescence, and Western blot.

RESULTS

Compared to the normal diet group, rats in the high-salt diet group had increases in systolic blood pressure and diastolic blood pressure (P < 0.05); collagen fiber accumulation was observed in the heart and kidney tissues (P < 0.01), accompanied by alterations in mitochondrial ultrastructure, reduced mitochondrial volume, and increased density of the mitochondrial double membrane. Additionally, there were significant increases in both iron content and malondialdehyde levels (P < 0.05). Immunofluorescence and Western blot results both indicated significant downregulation (P < 0.05) of xCT and GPX4 proteins associated with ferroptosis in the high-salt diet group.

CONCLUSIONS

Ferroptosis is involved in the damage and fibrosis of the heart and kidney tissues in salt-sensitive hypertensive rats.

摘要

背景

盐敏感性高血压往往更容易导致心脏和肾脏等靶器官受损。最近大量研究表明铁死亡与心血管疾病密切相关。因此，我们推测铁死亡可能与盐敏感性高血压的器官损伤密切相关。本研究旨在探讨铁死亡是否参与盐敏感性高血压大鼠心肌纤维化和肾纤维化的发生发展。

方法

选取10只7周龄雄性Dahl盐敏感性（Dahl-SS）大鼠，适应性喂养1周，然后随机分为两组，分别给予正常饮食（0.3%氯化钠，正常饮食组）或高盐饮食（8%氯化钠，高盐饮食组）8周。观察大鼠血压，并通过苏木精-伊红（HE）染色、Masson染色、普鲁士蓝染色、透射电子显微镜、组织铁含量检测、丙二醛含量检测、免疫荧光和蛋白质印迹法对Dahl-SS大鼠的心脏和肾脏进行分析。

结果

与正常饮食组相比，高盐饮食组大鼠的收缩压和舒张压升高（P<0.05）；心脏和肾脏组织中观察到胶原纤维堆积（P<0.01），同时伴有线粒体超微结构改变、线粒体体积减小和线粒体双层膜密度增加。此外，铁含量和丙二醛水平均显著升高（P<0.05）。免疫荧光和蛋白质印迹结果均表明，高盐饮食组中与铁死亡相关的xCT和GPX4蛋白显著下调（P<0.05）。