Wang Chuan-Zhi, Guo Heng-Zhi, Leng Jing-Zhi, Liang Zhi-De, Wang Jing-Tai, Luo Li-Jie, Wang Shi-Qiang, Yuan Yang
School of Physical Education, Qingdao University, Qingdao, China.
Cancer Institute of the Affiliated Hospital of Qingdao University and Qingdao Cancer Institute, Qingdao, China.
Heliyon. 2024 Feb 27;10(6):e27035. doi: 10.1016/j.heliyon.2024.e27035. eCollection 2024 Mar 30.
Doxorubicin (DOX) possesses strong anti-tumor effects but is limited by its irreversible cardiac toxicity. The relationship between exercise, a known enhancer of cardiovascular health, and DOX-induced cardiotoxicity has been a focus of recent research. Exercise has been suggested to mitigate DOX's cardiac harm by modulating the Yes-associated protein (YAP) and Signal transducer and activator of transcription 3 (STAT3) pathways, which are crucial in regulating cardiac cell functions and responses to damage. This study aimed to assess the protective role of exercise preconditioning against DOX-induced cardiac injury. We used Sprague-Dawley rats, divided into five groups (control, DOX, exercise preconditioning (EP), EP-DOX, and verteporfin + EP + DOX), to investigate the potential mechanisms. Our findings, including echocardiography, histological staining, Western blot, and q-PCR analysis, demonstrated that exercise preconditioning could alleviate DOX-induced cardiac dysfunction and structural damage. Notably, exercise preconditioning enhanced the nuclear localization and co-localization of YAP and STAT3. Our study suggests that exercise preconditioning may counteract DOX-induced cardiotoxicity by activating the YAP/STAT3 pathway, highlighting a potential therapeutic approach for reducing DOX's cardiac side effects.
阿霉素（DOX）具有很强的抗肿瘤作用，但受其不可逆心脏毒性的限制。运动作为一种已知的心血管健康增强因素，与DOX诱导的心脏毒性之间的关系一直是近期研究的重点。有研究表明，运动可通过调节Yes相关蛋白（YAP）和信号转导及转录激活因子3（STAT3）通路来减轻DOX对心脏的损害，这两条通路在调节心脏细胞功能和对损伤的反应中至关重要。本研究旨在评估运动预处理对DOX诱导的心脏损伤的保护作用。我们使用Sprague-Dawley大鼠，将其分为五组（对照组、DOX组、运动预处理组（EP）、EP-DOX组和维替泊芬+EP+DOX组），以研究潜在机制。我们的研究结果，包括超声心动图、组织学染色、蛋白质免疫印迹和定量聚合酶链反应分析，表明运动预处理可以减轻DOX诱导的心脏功能障碍和结构损伤。值得注意的是，运动预处理增强了YAP和STAT3的核定位及共定位。我们的研究表明，运动预处理可能通过激活YAP/STAT3通路来对抗DOX诱导的心脏毒性，这突出了一种减少DOX心脏副作用的潜在治疗方法。
