Elseweidy Mohamed M, Ali Sousou I, Shaheen Mohamed A, Abdelghafour Asmaa M, Hammad Sally K
Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
Department of Histology and Cell Biology, Faculty of Human Medicine, Zagazig University, Zagazig, 44519, Egypt.
Food Funct. 2023 Apr 3;14(7):3067-3082. doi: 10.1039/d2fo03570g.
Myocardial infarction (MI) is a major health problem associated with high morbidity and mortality. Recently, angiogenesis has emerged as a novel therapeutic approach against ischemic diseases including MI. Therefore, we aimed to investigate the potential angiogenic effects of vanillin (Van) both alone and in combination with pentoxifylline (PTX), and to examine the molecular mechanisms through which Van and PTX may ameliorate cardiac injury induced in rats including their effects on oxidative stress, inflammation and apoptosis which play a key role in MI pathogenesis. MI was induced in rats using isoproterenol (ISO) (150 mg kg, SC, twice at a 24 h interval). Then, rats were treated orally with Van (150 mg kg day), PTX (50 mg kg day) or Van + PTX combination. ISO-induced cardiac injury was characterized by cardiac hypertrophy, ST-segment elevation and elevated serum levels of troponin-I, creatine kinase-MB and lactate dehydrogenase. Cardiac levels of the antioxidant markers GSH and SOD and the antiapoptotic protein Bcl-2 were decreased. On the other hand, cardiac levels of the oxidative stress marker malonaldehyde, the inflammatory cytokines TNF-α, IL-6 and IL-1β, the proapoptotic protein Bax, and caspase-3 were increased. Moreover, the cardiac levels of p-Akt and HIF-1α and the mRNA expression levels of the angiogenic genes , and were increased. Treatment with either Van or PTX ameliorated ISO-induced changes and further upregulated Akt/HIF-1α/VEGF signaling. Furthermore, Van + PTX combination was more effective than monotherapy. These findings suggest a novel therapeutic potential of Van and PTX in ameliorating MI through enhancing cardiac angiogenesis and modulating oxidative stress, inflammation and apoptosis.
心肌梗死（MI）是一个与高发病率和死亡率相关的主要健康问题。最近，血管生成已成为一种针对包括MI在内的缺血性疾病的新型治疗方法。因此，我们旨在研究香草醛（Van）单独以及与己酮可可碱（PTX）联合使用时的潜在血管生成作用，并研究Van和PTX可能改善大鼠心脏损伤的分子机制，包括它们对氧化应激、炎症和凋亡的影响，这些因素在MI发病机制中起关键作用。使用异丙肾上腺素（ISO）（150 mg/kg，皮下注射，间隔24小时注射两次）诱导大鼠发生MI。然后，大鼠口服Van（150 mg/kg/天）、PTX（50 mg/kg/天）或Van + PTX组合。ISO诱导的心脏损伤表现为心脏肥大、ST段抬高以及血清肌钙蛋白-I、肌酸激酶-MB和乳酸脱氢酶水平升高。抗氧化标志物谷胱甘肽（GSH）和超氧化物歧化酶（SOD）以及抗凋亡蛋白Bcl-2的心脏水平降低。另一方面，氧化应激标志物丙二醛、炎性细胞因子肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）、促凋亡蛋白Bax和半胱天冬酶-3的心脏水平升高。此外，磷酸化Akt（p-Akt）和缺氧诱导因子-1α（HIF-1α）的心脏水平以及血管生成基因血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（bFGF）和血管生成素（ANG）的mRNA表达水平升高。单独使用Van或PTX治疗均可改善ISO诱导的变化，并进一步上调Akt/HIF-1α/VEGF信号通路。此外，Van + PTX组合比单一疗法更有效。这些发现表明Van和PTX在通过增强心脏血管生成以及调节氧化应激、炎症和凋亡来改善MI方面具有新的治疗潜力。
