Xie Mengjie, Guo Fuding, Song Lingpeng, Tan Wuping, Han Xinrui, Xu Saiting, Li Xujun, Wang Yijun, Wang Yueyi, Zhou Liping, Zhou Xiaoya, Jiang Hong, Yu Lilei
Department of Cardiology, Renmin Hospital of Wuhan University; Institute of Molecular Medicine, Renmin Hospital of Wuhan University; Hubei Key Laboratory of Autonomic Nervous System Modulation; Taikang Center for Life and Medical Sciences, Wuhan University; Cardiac Autonomic Nervous System Research Center of Wuhan University; Hubei Key Laboratory of Cardiology; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China.
iScience. 2024 Feb 13;27(3):109163. doi: 10.1016/j.isci.2024.109163. eCollection 2024 Mar 15.
Doxorubicin (Dox) poses a considerable threat to patients owing to its cardiotoxicity, thus limiting its clinical utility. Optimal cardioprotective intervention strategies are needed to suppress tumor growth but also minimize cardiac side effects. Here, we showed that tragus vagus nerve stimulation (tVNS) improved the imbalanced autonomic tone, ameliorated impaired cardiac function and fibrosis, attenuated myocyte apoptosis, and mitochondrial dysfunction compared to those in the Dox group. The beneficial effects were attenuated by methyllycaconitine citrate (MLA). The transcript profile revealed that there were 312 differentially expressed genes and the protection of tVNS and retardation of MLA were related to inflammatory response and NADPH oxidase activity. In addition, tVNS synergizing with Dox inhibited tumor growth and lung metastasis and promoted apoptosis of tumor cells in an anti-tumor immunity manner. These results indicated that non-invasive neuromodulation can play a dual role in preventing Dox-induced cardiotoxicity and suppressing tumor growth through inflammation and oxidative stress.
由于具有心脏毒性，阿霉素（Dox）对患者构成了相当大的威胁，从而限制了其临床应用。需要最佳的心脏保护干预策略来抑制肿瘤生长，同时将心脏副作用降至最低。在此，我们表明，与阿霉素组相比，耳屏迷走神经刺激（tVNS）改善了自主神经张力失衡，减轻了心脏功能受损和纤维化，减少了心肌细胞凋亡和线粒体功能障碍。柠檬酸甲基利卡多因（MLA）减弱了这些有益作用。转录谱显示有312个差异表达基因，tVNS的保护作用和MLA的抑制作用与炎症反应和NADPH氧化酶活性有关。此外，tVNS与阿霉素协同作用，以抗肿瘤免疫方式抑制肿瘤生长和肺转移，并促进肿瘤细胞凋亡。这些结果表明，非侵入性神经调节可通过炎症和氧化应激在预防阿霉素诱导的心脏毒性和抑制肿瘤生长方面发挥双重作用。
