Zhang Yuxi, Zhan Junbiao, Qiu Zhen, Tian Hao, Lei Shaoqing, Huang Qin, Xue Rui, Sun Qian, Xia Zhongyuan
Department of Anesthesiology, Wuhan University, Renmin Hospital, Wuhan, China.
Department of Anesthesiology, Hubei University of Medicine, Renmin Hospital, Shiyan, China.
Sci Rep. 2025 May 5;15(1):15651. doi: 10.1038/s41598-025-00112-4.
Myocardial cold ischemia/reperfusion (I/R) injury is an inevitable consequence of heart transplantation, significantly affecting survival rates and therapeutic outcomes. Growth Differentiation Factor 15 (GDF15) has been shown to regulate GPX4-mediated ferroptosis, playing a critical role in mitigating I/R injury. Meanwhile, verbascoside (VB), an active compound extracted from the herbaceous plant, has demonstrated myocardial protective effects. In this study, heart transplantation was performed using a modified non-suture cuff technique, with VB administered at a dose of 20 mg/kg/day via intraperitoneal injection for 3 days in vivo. In vitro, cardiomyocytes were pretreated with 50 µg/ml VB for 24 h. VB treatment significantly reduced histopathological injury, decreased myocardial injury markers, and inhibited ferroptosis and oxidative stress during myocardial cold I/R injury in vivo. In vitro experiments further demonstrated that GDF15 alleviates ferroptosis induced by hypoxic reoxygenation by upregulating GPX4. Therefore, it is concluded that VB preconditioning can effectively reduce ferroptosis induced by myocardial cold I/R after heterotopic heart transplantation, possibly through up-regulation of GDF15/GPX4/SLC7A11 pathway.
心肌冷缺血/再灌注（I/R）损伤是心脏移植不可避免的后果，显著影响生存率和治疗效果。生长分化因子15（GDF15）已被证明可调节GPX4介导的铁死亡，在减轻I/R损伤中起关键作用。同时，毛蕊花糖苷（VB）是从草本植物中提取的一种活性化合物，已显示出心肌保护作用。在本研究中，采用改良的非缝合袖套技术进行心脏移植，在体内通过腹腔注射以20mg/kg/天的剂量给予VB，持续3天。在体外，心肌细胞用50μg/ml VB预处理24小时。VB治疗显著减轻了体内心肌冷I/R损伤期间的组织病理学损伤，降低了心肌损伤标志物，并抑制了铁死亡和氧化应激。体外实验进一步证明，GDF15通过上调GPX4减轻缺氧复氧诱导的铁死亡。因此，得出结论，VB预处理可有效减少异位心脏移植后心肌冷I/R诱导的铁死亡，可能是通过上调GDF15/GPX4/SLC7A11通路实现的。
