Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
PeerJ. 2023 May 3;11:e15280. doi: 10.7717/peerj.15280. eCollection 2023.
Heart failure with preserved ejection fraction (HFpEF) is a public health problem worldwide. Treatments for the patients with HFpEF are not satisfactory because there is no unified understanding of the pathological mechanism of HFpEF. This study aims at investigating the potential pathological mechanism for the effective diagnosis and treatment of HFpEF.
Ten adult male Dahl salt sensitive rats (180-200 g) were divided into control and model groups. The rats in model group were fed with high salt diet (8% NaCl) to induce HFpEF for this comparative study. Behavioral changes, biochemical parameters, and histopathological changes of the rats were detected. iTRAQ technology combined with bioinformatics analysis was employed to study the differentially expressed proteins (DEPs) and their enrichment in signaling pathways.
Echocardiography detection showed decreased LVEF, indicating impaired cardiac function ( < 0.01), increased LVPWd, indicating ventricular wall hypertrophy ( < 0.05), prolonged duration of IVRT and decreased E/A ratio, indicating diastolic dysfunction ( < 0.05) of the rats in model group. 563 DEPs were identified in the rats of both groups, with 243 up-regulated and 320 down-regulated. The expression of PPAR signaling pathway in the rats of model group was down-regulated, with PPAR most significantly decreased (91.2%) ( < 0.01), PPAR obviously decreased (63.60%) ( < 0.05), and PPAR/ decreased (45.33%) ( < 0.05). The DEPs enriched in PPAR signaling pathway were mainly related to such biological processes as fatty acid beta-oxidation, such cellular components as peroxisome, and such molecular functions as lipid binding.
NaCl high salt diet is one of the factors to increase the incidence of HFpEF in rats. PPAR, PPAR and PPAR / might be the targets of HFpEF. The findings may provide a theoretical basis for the treatment of HFpEF in clinical practice.
射血分数保留的心力衰竭（HFpEF）是全球范围内的一个公共卫生问题。由于对 HFpEF 的病理机制尚未达成统一认识，因此针对该类患者的治疗效果并不理想。本研究旨在探讨 HFpEF 的潜在病理机制，以期为其有效诊断和治疗提供依据。
将 10 只成年雄性 Dahl 盐敏感大鼠（180-200g）随机分为对照组和模型组。模型组大鼠给予高盐饮食（8%NaCl）诱导 HFpEF，比较两组大鼠的行为学改变、生化指标及组织病理学变化。采用 iTRAQ 技术结合生物信息学分析方法，研究两组大鼠差异表达蛋白（DEPs）及其在信号通路中的富集情况。
超声心动图检测结果显示，模型组大鼠左心室射血分数（LVEF）降低，提示心功能受损（<0.01），左室后壁厚度（LVPWd）增加，提示心室壁肥厚（<0.05），室间隔舒张末期厚度（IVRT）延长，E/A 比值降低，提示舒张功能障碍（<0.05）。两组大鼠共鉴定出 563 个 DEPs，其中 243 个上调，320 个下调。模型组大鼠的过氧化物酶体增殖物激活受体（PPAR）信号通路表达下调，其中 PPAR 显著下调（91.2%）（<0.01），PPAR 明显下调（63.60%）（<0.05），PPAR/ 下调（45.33%）（<0.05）。PPAR 信号通路富集的 DEPs 主要涉及脂肪酸β氧化等生物学过程，细胞成分主要为过氧化物酶体，分子功能主要为脂质结合。
高盐饮食是增加大鼠 HFpEF 发病率的因素之一。PPAR、PPAR 和 PPAR/可能是 HFpEF 的作用靶点。研究结果可为临床治疗 HFpEF 提供理论依据。
