College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, PR China.
Department of Cardiovascular Medicine, The General Hospital of Western Theater Command PLA, Chengdu, PR China ; and.
J Cardiovasc Pharmacol. 2021 Apr 1;77(4):491-500. doi: 10.1097/FJC.0000000000000989.
The incidence of myocardial dysfunction caused by sepsis is high, and the mortality of patients with sepsis can be significantly increased. During sepsis, oxidative stress and inflammation can lead to severe organ dysfunction. Flavone chrysin is one of the indispensable biological active ingredients for different fruits and vegetables and has antioxidant and anti-inflammatory properties. However, it is not clear whether chrysin is an effective treatment for heart dysfunction caused by sepsis. We found that it had protective effects against the harmful effects caused by LPS, manifested in improved survival, normalized cardiac function, improved partial pathological scores of myocardial tissue, and remission of apoptosis, as well as reduced oxidative stress and inflammation. Mechanism studies have found that chrysin is an important antioxidant protein, a key regulator of heme oxygenase 1 (HO-1). We found that HO-1 levels were increased after LPS intervention, and chrysin further increased HO-1 levels, along with the addition of Nrf2, a regulator of antioxidant proteins. Pretreatment with PD98059, an extracellular signal-regulated kinase-specific inhibitor, blocked chrysin-mediated phosphorylation of Nrf2 and the nuclear translocation of Nrf2. The protective effect of chrysin on sepsis-induced cardiac dysfunction was blocked by ZnPP, which is a HO-1 blocker. Chrysin increased antioxidant activity and reduced markers of oxidative stress (SOD and MDA) and inflammation (MPO and IL-1β), all of which were blocked by ZnPP. This indicates that HO-1 is the upstream molecule regulating the protective effect of chrysin. Thus, by upregulation of HO-1, chrysin protects against LPS-induced cardiac dysfunction and inflammation by inhibiting oxidative stress.
脓毒症引起的心肌功能障碍发生率较高，可显著增加脓毒症患者的死亡率。脓毒症时氧化应激和炎症可导致严重的器官功能障碍。白杨素是水果和蔬菜中不可缺少的生物活性成分之一，具有抗氧化和抗炎作用。然而，尚不清楚白杨素有否是治疗脓毒症引起的心脏功能障碍的有效药物。我们发现它对 LPS 引起的有害作用有保护作用，表现在存活率提高、心功能正常化、心肌组织部分病理评分改善、细胞凋亡减轻，以及氧化应激和炎症减少。机制研究发现，白杨素是一种重要的抗氧化蛋白，血红素加氧酶 1 (HO-1)的关键调节剂。我们发现 LPS 干预后 HO-1 水平增加，白杨素进一步增加 HO-1 水平，同时增加抗氧化蛋白的调节剂 Nrf2。用细胞外信号调节激酶特异性抑制剂 PD98059 预处理可阻断白杨素介导的 Nrf2 磷酸化和 Nrf2 的核转位。HO-1 阻断剂 ZnPP 阻断了白杨素对脓毒症诱导的心脏功能障碍的保护作用。白杨素增加了抗氧化活性，降低了氧化应激标志物（SOD 和 MDA）和炎症标志物（MPO 和 IL-1β），ZnPP 阻断了这些作用。这表明 HO-1 是调节白杨素保护作用的上游分子。因此，通过 HO-1 的上调，白杨素通过抑制氧化应激来保护 LPS 诱导的心脏功能障碍和炎症。
