PDF(Pubmed)
Abstract：
Acute myocardial injury (AMI) is often secondary to sepsis, which is a life-threatening disease associated with severe cardiac inflammation. Narciclasine, a plant alkaloid isolated from different members of the Amaryllidaceae family, has been extensively characterized as an antitumor and anti-inflammatory compound. In addition, autophagy is critical for sepsis-induced myocardial injury. However, the role and mechanism of autophagy by which narciclasine confers cardioprotection are still unclear. The present study aimed to investigate the underlying mechanism by which narciclasine affects the pathogenesis of sepsis-induced myocardial injury. Narciclasine effectively attenuated LPS-induced myocardial inflammation in vitro and in vivo. In addition, narciclasine protected cardiac function and suppressed the expression of inflammatory cytokines in LPS-induced heart tissue. Furthermore, narciclasine upregulated LPS-induced autophagic activity, and the autophagy inhibitor 3-MA abrogated narciclasine-mediated protection against LPS-induced AMI. Importantly, narciclasine exerted an inhibitory effect on the JNK signaling pathway, and JNK activity was tightly associated with narciclasine-induced autophagy and the consequent protective effects during AMI. Taken together, our findings indicate that narciclasine protects against LPS-induced AMI by inducing JNK-dependent autophagic flux; hence, narciclasine may be an effective and novel agent for the clinical treatment of sepsis-induced myocardial injury.
摘要：
急性心肌损伤（AMI）通常继发于败血症，这是一种与严重心脏炎症相关的危及生命的疾病。Narciclasine,一种从石豆科不同成员中分离出的植物生物碱，已被广泛表征为抗肿瘤和抗炎化合物。此外,自噬是脓毒症心肌损伤的关键。然而,自噬在沙西拉辛赋予心脏保护作用的作用和机制尚不清楚。本研究旨在探讨沙西拉辛影响脓毒症心肌损伤的发病机制。Narciclasine在体外和体内可有效减轻LPS诱导的心肌炎症。此外,在LPS诱导的心脏组织中，沙西拉辛具有保护心功能和抑制炎症因子表达的作用。此外，沙西拉辛上调LPS诱导的自噬活性，自噬抑制剂3-MA废除了那西拉辛介导的对LPS诱导的AMI的保护作用。重要的是,沙西拉辛对JNK信号通路有抑制作用，JNK活性与沙西拉辛诱导的自噬及其在AMI期间的保护作用密切相关。一起来看,我们的发现表明，沙西拉辛通过诱导JNK依赖性自噬通量来保护LPS诱导的AMI；因此，沙西拉辛可能是临床治疗脓毒症心肌损伤的一种有效的新药。
