Saghaei Elham, Ataei-Goujani Hosein, Amini-Khoei Hossein, Anjomshoa Maryam, Najafi-Chaleshtori Somayeh
Department of Physiology and Pharmacology, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Res Pharm Sci. 2025 Aug 25;20(4):524-534. doi: 10.4103/RPS.RPS_234_24. eCollection 2025 Aug.
Selegiline, an irreversible monoamine oxidase B inhibitor, has been shown to have potential in reducing cell damage. The present study design focused on the cardioprotective effect of selegiline and its possible mechanism of action through phosphoinositide-3-kinase/serine-threonine kinase AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway.
Myocardial ischemia was induced in male Wistar rats by isoproterenol injection. Selegiline was administered (2 and 5 mg/kg) for 14 days. Electrocardiogram (ECG) parameters and serum markers were measured. PI3K, AKT, and mTOR protein expression and histopathological examination of cardiac tissue were performed. All data were analyzed using GraphPad Prism.
FINDINGS/RESULTS: Pre-treatment with selegiline (5 mg/kg) effectively restored ECG parameters changes and cardiac serum markers elevation seen in isoproterenol receiving groups, with a reduction of lactate dehydrogenase by 55.2% and creatine kinase-myoglobin bind level by 80.1%. Histopathological examination of cardiac tissue revealed successful prevention of fibrosis and inflammation following isoproterenol administration in selegiline-treated groups. Furthermore, western blot analysis demonstrated that pre-treatment with selegiline (5 mg/kg) increased the proportion of phosphorylated to non-phosphorylated proteins involved in the PI3K/AKT/mTOR signaling pathway.
Selegiline administration could protect against myocardial ischemia, induced following isoproterenol injection, which is mediated through PI3K/AKT/mTOR signaling pathways. However, future study needs to focus more on the exact protective route of selegiline action.
司来吉兰是一种不可逆的单胺氧化酶B抑制剂，已被证明具有减轻细胞损伤的潜力。本研究设计聚焦于司来吉兰的心脏保护作用及其通过磷酸肌醇-3-激酶/丝氨酸-苏氨酸激酶AKT/雷帕霉素哺乳动物靶点（PI3K/AKT/mTOR）通路的可能作用机制。
通过注射异丙肾上腺素在雄性Wistar大鼠中诱导心肌缺血。给予司来吉兰（2和5mg/kg），持续14天。测量心电图（ECG）参数和血清标志物。进行PI3K、AKT和mTOR蛋白表达以及心脏组织的组织病理学检查。所有数据使用GraphPad Prism进行分析。
用司来吉兰（5mg/kg）预处理可有效恢复异丙肾上腺素给药组中出现的ECG参数变化和心脏血清标志物升高，乳酸脱氢酶降低55.2%，肌酸激酶-肌红蛋白结合水平降低80.1%。心脏组织的组织病理学检查显示，在司来吉兰治疗组中，异丙肾上腺素给药后成功预防了纤维化和炎症。此外，蛋白质印迹分析表明，用司来吉兰（5mg/kg）预处理增加了PI3K/AKT/mTOR信号通路中磷酸化蛋白与非磷酸化蛋白的比例。
给予司来吉兰可预防异丙肾上腺素注射后诱导的心肌缺血，这是通过PI3K/AKT/mTOR信号通路介导的。然而，未来的研究需要更多地关注司来吉兰作用的确切保护途径。
