Chrysin Ameliorates Sepsis-Induced Cardiac Dysfunction Through Upregulating Nfr2/Heme Oxygenase 1 Pathway
Chrysin Ameliorates Sepsis-Induced Cardiac Dysfunction Through Upregulating Nfr2/Heme Oxygenase 1 Pathway
复制标题
白杨素通过上调 Nfr2/血红素加氧酶 1 通路改善脓毒症引起的心脏功能障碍
DOI：
10.1097/fjc.0000000000000989
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发表时间：
2021-04-01
影响因子：
3
通讯作者：
Yang Yongjian
中科院分区：
文献类型：
--
作者：
Li Xingyue;Li Shuang;Yang Yongjian
脓毒症引起心肌功能障碍的发生率高，脓毒症患者的死亡率可明显增加。在脓毒症期间，氧化应激和炎症可导致严重的器官功能障碍。黄酮白杨素是不同水果和蔬菜不可缺少的生物活性成分之一，具有抗氧化和抗炎特性。然而，白杨素是否是脓毒症引起的心功能不全的有效治疗方法尚不清楚。我们发现，它对LPS引起的有害影响具有保护作用，表现在提高存活率，使心脏功能正常化，改善心肌组织的部分病理评分，缓解细胞凋亡，以及减少氧化应激和炎症。机制研究发现白杨素是一种重要的抗氧化蛋白，是血红素加氧酶1（HO-1）的关键调节因子。我们发现HO-1水平在LPS干预后增加，白杨素进一步增加HO-1水平，沿着加入抗氧化蛋白调节剂Nrf 2。细胞外信号调节激酶特异性抑制剂PD 98059预处理可阻断白杨素介导的Nrf 2磷酸化和Nrf 2核转位。白杨素对脓毒症心功能不全的保护作用可被HO-1阻断剂ZnPP阻断。胡萝卜素增加抗氧化活性，降低氧化应激（SOD和MDA）和炎症（MPO和IL-1 β）的标志物，所有这些都被ZnPP阻断。这表明HO-1是调控白杨素保护作用的上游分子。因此，通过上调HO-1，白杨素通过抑制氧化应激来防止LPS诱导的心脏功能障碍和炎症。
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-1 beta), 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.