Accumulating evidence has highlighted the role of ferroptosis, a novel type of programmed cell death involved in the pathological process of myocardial infarction (MI). However, the underlying mechanism of ferroptosis in mediating MI is complicated that needs to be further investigated. Salvianolic acid B (Sal B) extracted from the traditional Chinese medicine (TCM) herb Salvia miltiorrhiza possesses pharmacological function against MI, which provides us with a new direction to explore the effect of Sal B on ferroptosis after myocardial ischemic injury. In the present study, iron accumulation and expression levels of ferroptosis-related proteins in MI rats altered in a time-dependent manner. Importantly, treatment of ferroptosis inhibitors ferrostatin-1 (Fer-1) or deferoxamine (DFO) reversed typical changes of ferroptosis, including iron overload, lipid peroxide accumulation, mitochondrial damage, and specific expression levels of ferroptosis-related proteins, thereby alleviating myocardial injury in rats. Similar results were observed in Sal B-treated MI rats in a dose-dependent manner. In addition, NFE2-related factor 2 (Nrf2) was strongly activated by the treatment of Sal B. In vivo knockdown of Nrf2 in MI rats enhanced ferroptosis and damaged the protective effect of Sal B on MI. Furthermore, Sal B administration was unable to significantly reverse expression levels of target genes of Nrf2 that were associated with iron homeostasis and oxidative stress (e.g., HO-1, xCT, Gpx4, Fth1, and Fpn1) in MI rats after knockdown of Nrf2. Taken together, Sal B contributed to protecting MI by inhibiting ferroptosis via activating the Nrf2 signaling pathway.

越来越多的证据强调了铁死亡的作用，这是一种参与心肌梗塞 (MI) 病理过程的新型程序性细胞死亡。然而，铁死亡介导心肌梗死的潜在机制很复杂，需要进一步研究。从中药 (TCM)丹参中提取的丹酚酸 B (Sal B)具有抗心肌梗死的药理作用，为我们探索Sal B对心肌缺血损伤后铁死亡的影响提供了新的方向。在本研究中，MI 大鼠中铁死亡相关蛋白的铁积累和表达水平以时间依赖性方式发生变化。重要的是，铁死亡抑制剂 ferrostatin-1 (Fer-1) 或去铁胺 (DFO) 的治疗逆转了铁死亡的典型变化，包括铁过载、脂质过氧化物积累、线粒体损伤和铁死亡相关蛋白的特异性表达水平，从而减轻心肌损伤在大鼠中。在 Sal B 治疗的 MI 大鼠中以剂量依赖性方式观察到类似的结果。此外，NFE2 相关因子 2 (Nrf2) 被 Sal B 处理强烈激活。MI大鼠中Nrf2的敲低增强了铁死亡并破坏了Sal B对MI的保护作用。此外，在敲除 Nrf2 后，Sal B 给药无法显着逆转 MI 大鼠中与铁稳态和氧化应激相关的 Nrf2 靶基因（例如，HO-1、xCT、Gpx4、Fth1 和 Fpn1）的表达水平。总之，Sal B 通过激活 Nrf2 信号通路抑制铁死亡，从而有助于保护 MI。