Yang Jing, Zhang Chun-Rui, Li Zi-Xuan, Gao Yi-He, Jiang Li, Zhang Jing, Wang Peng-Yue, Liu Tong
Puyang Medical College, Puyang, 457000, China.
Cardiovascular Laboratory of Xinxiang, Xinxiang, 453003, China.
Eur J Pharmacol. 2025 Jun 15;997:177477. doi: 10.1016/j.ejphar.2025.177477. Epub 2025 Mar 8.
Myocardial aging, involving oxidative stress, mitochondrial dysfunction, and cellular senescence, is crucial to DOX - induced heart failure. DOX has dose - dependent cardiotoxicity. Sper a natural polyamine with antioxidant and anti - aging effects, remains unstudied in this context.
This study hypothesizes Sper can alleviate DOX - induced heart failure by curbing myocardial aging and oxidative stress. It aims to assess Sper's protective impacts on cardiac function, pathology, oxidative stress, mitochondrial damage, and aging in a rat model, using captopril as a control.
80 male Sprague Dawley rats were assigned to 8 groups: normal control, 150 mg/kg Sper, DOX, and DOX +10/50/100/150 mg/kg Sper, DOX +30 mg/kg captopril. DOX was given intraperitoneally at 15 mg/kg total dose, while Sper or captopril was administered daily via gavage for six weeks. Cardiac function was evaluated using echocardiography, and histopathological changes, oxidative stress markers, mitochondrial damage, and myocardial aging were assessed via H&E staining, immunofluorescence, Western blot, and electron microscopy.
Sper boosted cardiac function in DOX - treated rats, upping EF and SV, and lessening cardiac tissue damage. It cut oxidative stress by reducing MDA levels and boosting SOD activity. Sper also eased mitochondrial damage by enhancing mitochondrial membrane potential and cutting mitochondrial fission proteins (Drp1 and Fis1). Plus, Sper held back myocardial aging by trimming β - galactosidase activity and downregulating p - P53 and p21 expression. At 150 mg/kg/day, Sper worked much like 30 mg/kg/day captopril.
Sper effectively eased DOX - induced heart failure by targeting oxidative stress and aging, showing potential as an adjunct therapy for DOX - related cardiotoxicity. Future research should explore Sper's molecular mechanisms and clinical efficacy.
心肌衰老涉及氧化应激、线粒体功能障碍和细胞衰老，是多柔比星诱导心力衰竭的关键因素。多柔比星具有剂量依赖性心脏毒性。精胺是一种具有抗氧化和抗衰老作用的天然多胺，在这方面尚未得到研究。
本研究假设精胺可通过抑制心肌衰老和氧化应激来减轻多柔比星诱导的心力衰竭。其旨在以卡托普利作为对照，评估精胺对大鼠模型心脏功能、病理学、氧化应激、线粒体损伤和衰老的保护作用。
80只雄性Sprague Dawley大鼠被分为8组：正常对照组、150mg/kg精胺组、多柔比星组以及多柔比星+10/50/100/150mg/kg精胺组、多柔比星+30mg/kg卡托普利组。多柔比星以15mg/kg的总剂量腹腔注射，而精胺或卡托普利每天经口灌胃给药六周。使用超声心动图评估心脏功能，并通过苏木精-伊红染色、免疫荧光、蛋白质印迹法和电子显微镜评估组织病理学变化、氧化应激标志物、线粒体损伤和心肌衰老。
精胺改善了多柔比星处理大鼠的心脏功能，提高了射血分数和每搏输出量，并减轻了心脏组织损伤。它通过降低丙二醛水平和提高超氧化物歧化酶活性来减轻氧化应激。精胺还通过增强线粒体膜电位和减少线粒体分裂蛋白（动力相关蛋白1和线粒体分裂因子1）来缓解线粒体损伤。此外，精胺通过降低β-半乳糖苷酶活性和下调磷酸化P53和p21表达来抑制心肌衰老。在150mg/kg/天的剂量下，精胺的作用与30mg/kg/天的卡托普利相似。
精胺通过针对氧化应激和衰老有效减轻了多柔比星诱导的心力衰竭，显示出作为多柔比星相关心脏毒性辅助治疗的潜力。未来的研究应探索精胺的分子机制和临床疗效。
