Abstract：
High-altitude myocardial injury (HAMI) represents a critical form of altitude illness for which effective drug therapies are generally lacking. Notoginsenoside R1, a prominent constituent derived from Panax notoginseng, has demonstrated various cardioprotective properties in models of myocardial ischemia/reperfusion injury, sepsis-induced cardiomyopathy, cardiac fibrosis, and myocardial injury. The potential utility of notoginsenoside R1 in the management of HAMI warrants prompt investigation. Following the successful construction of a HAMI model, a series of experimental analyses were conducted to assess the effects of notoginsenoside R1 at dosages of 50 mg/Kg and 100 mg/Kg. The results indicated that notoginsenoside R1 exhibited protective effects against hypoxic injury by reducing levels of CK, CK-MB, LDH, and BNP, leading to improved cardiac function and decreased incidence of arrhythmias. Furthermore, notoginsenoside R1 was found to enhance Nrf2 nuclear translocation, subsequently regulating the SLC7A11/GPX4/HO-1 pathway and iron metabolism to mitigate ferroptosis, thereby mitigating cardiac inflammation and oxidative stress induced by high-altitude conditions. In addition, the application of ML385 has confirmed the involvement of Nrf2 nuclear translocation in the therapeutic approach to HAMI. Collectively, the advantageous impacts of notoginsenoside R1 on HAMI have been linked to the suppression of ferroptosis via Nrf2 nuclear translocation signaling.
摘要：
高原心肌损伤（HAMI）是高原疾病的一种关键形式，通常缺乏有效的药物治疗。三七皂苷R1，一种来自三七的重要成分，在心肌缺血/再灌注损伤模型中已经证明了各种心脏保护特性，脓毒症诱发的心肌病，心脏纤维化，和心肌损伤。三七皂苷R1在HAMI管理中的潜在效用值得研究。在成功构建HAMI模型之后，进行了一系列实验分析，以评估三七皂苷R1在50mg/Kg和100mg/Kg剂量下的作用。结果表明，三七皂苷R1通过降低CK水平对低氧损伤具有保护作用，CK-MB,LDH,和BNP,导致改善心脏功能和降低心律失常的发生率。此外，发现三七皂苷R1增强Nrf2核易位，随后调节SLC7A11/GPX4/HO-1通路和铁代谢以减轻铁凋亡，从而减轻高海拔条件引起的心脏炎症和氧化应激。此外,ML385的应用证实了Nrf2核易位参与了HAMI的治疗方法。总的来说，三七皂苷R1对HAMI的有利影响与通过Nrf2核易位信号抑制铁凋亡有关。
