Biochemistry Department, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
Histology and Cell Biology Department, Faculty of Human Medicine, Zagazig University, Zagazig, 44519, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Jul;397(7):4677-4692. doi: 10.1007/s00210-023-02904-9. Epub 2023 Dec 19.
Ischemic heart diseases such as myocardial infarction (MI) are a global health problem and a leading cause of mortality worldwide. Angiogenesis is an important approach for myocardial healing following ischemia. Thus, this study aimed to explore the potential cardiac angiogenic effects of selenium (Se), alone and in combination with the tumor necrosis factor-alpha inhibitor, pentoxifylline (PTXF), via Akt/HIF-1α signaling. MI was induced in rats using two subcutaneous doses of isoprenaline (ISP) at a 24-h interval (150 mg/kg). One week later, rats were orally given Se (150 µg/kg/day), PTXF (50 mg/kg/day), or Se/PTXF combination. ISP-induced myocardial damage was evident by increased HW/TL ratios, ST segment elevation, and increased serum levels of CK-MB, LDH, and troponin-I. ISP increased the cardiac levels of the lipid peroxidation marker MDA; the pro-inflammatory cytokines IL-6, IL-1β, and TNF-α; and the pro-apoptotic protein Bax and caspase-3. In contrast, the cardiac levels of the antioxidant markers GSH and SOD and the anti-apoptotic marker Bcl-2 were reduced. Furthermore, ISP markedly increased the cardiac levels of p-Akt and HIF-1α proteins and the cardiac gene expression of ANGPT-1, VEGF, and FGF-2. Treatment with Se both alone and in combination with PTXF ameliorated the ISP-induced myocardial damage and further increased cardiac angiogenesis via Akt/HIF-1α signaling. Se/PTXF combined therapy was more beneficial than individual treatments. Our study revealed for the first time the cardiac angiogenic effects of Se both alone and in combination with PTXF in myocardial infarction, suggesting that both may be promising candidates for clinical studies.
缺血性心脏病，如心肌梗死（MI），是一个全球性的健康问题，也是全球死亡的主要原因。血管生成是缺血后心肌修复的重要方法。因此，本研究旨在通过 Akt/HIF-1α 信号通路，单独及联合使用肿瘤坏死因子-α 抑制剂己酮可可碱（PTXF），探索硒（Se）的潜在心脏血管生成作用。通过两次皮下注射异丙肾上腺素（ISP）（150mg/kg）间隔 24 小时诱导大鼠 MI（150μg/kg/天），PTXF（50mg/kg/天）或 Se/PTXF 组合。ISP 导致心肌损伤，表现为 HW/TL 比值升高、ST 段抬高以及血清 CK-MB、LDH 和肌钙蛋白 I 水平升高。ISP 增加了心脏脂质过氧化标志物 MDA 的水平；促炎细胞因子 IL-6、IL-1β 和 TNF-α；以及促凋亡蛋白 Bax 和 caspase-3。相反，心脏抗氧化标记物 GSH 和 SOD 的水平以及抗凋亡标记物 Bcl-2 的水平降低。此外，ISP 显著增加了心脏 p-Akt 和 HIF-1α 蛋白的水平以及心脏 ANGPT-1、VEGF 和 FGF-2 的基因表达。单独或联合使用 Se 可改善 ISP 引起的心肌损伤，并通过 Akt/HIF-1α 信号通路进一步增加心脏血管生成。Se/PTXF 联合治疗比单独治疗更有益。本研究首次揭示了 Se 单独及联合 PTXF 在心肌梗死中的心脏血管生成作用，表明两者均可能是临床研究的有前途的候选药物。
