Edaravone Improves Septic Cardiac Function by Inducing an HIF-1α/HO-1 Pathway.
Edaravone Improves Septic Cardiac Function by Inducing an HIF-1α/HO-1 Pathway.
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依达拉奉通过诱导 HIF-1 α/HO-1 通路改善脓毒症心脏功能
DOI：
10.1155/2018/5216383
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发表时间：
2018
影响因子：
--
通讯作者：
Xiao F
中科院分区：
文献类型：
--
作者：
He C;Zhang W;Li S;Ruan W;Xu J;Xiao F
脓毒性心肌功能障碍在脓毒症患者中仍然普遍存在并提高了死亡率。在脓毒症期间，组织承受巨大的氧化应激，这对器官功能障碍至关重要。依达拉奉是一种有效的自由基清除剂，已被证明对涉及缺氧诱导因子- (HIF-) 1的缺血性损伤有益，HIF- 1是一种重要的抗氧化蛋白血红素加氧酶- (HO-) 1的关键调节因子。然而，其在脓毒性心肌功能障碍中的作用尚不清楚。我们假设依达拉奉可能通过诱导HIF-1/HO-1通路来预防脓毒性心肌功能障碍。在进行CLP之前，大鼠进行盲肠结扎穿刺（CLP），同时输注依达拉奉或不输注依达拉奉三种剂量（分别为50、100或200 mg/kg）， CLP之后，腹腔注射HIF-1α拮抗剂ME （15 mg/kg）。CLP后大鼠出现心功能障碍，心肌变形，脂质过氧化增强，心肌凋亡和炎症增加，心肌过氧化氢酶、HIF-1α和HO-1活性降低。依达拉奉预处理以剂量依赖性逆转了这一变化，其中大剂量对脓毒症大鼠心功能和生存率的改善最为有效。然而，ME对HIF-1α的抑制破坏了高剂量依达拉奉的有益作用，降低了未经治疗的脓毒症大鼠的存活率。综上所述，依达拉奉通过诱导HIF-1α/HO-1通路，抑制氧化应激，保护心脏免受脓毒性心肌损伤和功能障碍。
Septic myocardial dysfunction remains prevalent and raises mortality rate in patients with sepsis. During sepsis, tissues undergo tremendous oxidative stress which contributes critically to organ dysfunction. Edaravone, a potent radical scavenger, has been proved beneficial in ischemic injuries involving hypoxia-inducible factor- (HIF-) 1, a key regulator of a prominent antioxidative protein heme oxygenase- (HO-) 1. However, its effect in septic myocardial dysfunction remains unclarified. We hypothesized that edaravone may prevent septic myocardial dysfunction by inducing the HIF-1/HO-1 pathway. Rats were subjected to cecal ligation and puncture (CLP) with or without edaravone infusion at three doses (50, 100, or 200 mg/kg, resp.) before CLP and intraperitoneal injection of the HIF-1α antagonist, ME (15 mg/kg), after CLP. After CLP, rats had cardiac dysfunction, which was associated with deformed myocardium, augmented lipid peroxidation, and increased myocardial apoptosis and inflammation, along with decreased activities of catalase, HIF-1α, and HO-1 in the myocardium. Edaravone pretreatment dose-dependently reversed the changes, of which high dose most effectively improved cardiac function and survival rate of septic rats. However, inhibition of HIF-1α by ME demolished the beneficial effects of edaravone at high dose, reducing the survival rate of the septic rats without treatments. Taken together, edaravone, by inducing the HIF-1α/HO-1 pathway, suppressed oxidative stress and protected the heart against septic myocardial injury and dysfunction.
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DOI：
10.1124/jpet.103.053595
发表时间：
2003-10-01
影响因子：
3.5
作者：
Kono, H;Asakawa, M;Matsumoto, Y
通讯作者：
Matsumoto, Y
影响因子：
4.7
作者：
Lei S;Zhang P;Li W;Gao M;He X;Zheng J;Li X;Wang X;Wang N;Zhang J;Qi C;Lu H;Chen X;Liu Y
通讯作者：
Liu Y
影响因子：
5.7
作者：
Chen, Huai-Min;Liou, Shu-Fen;Yeh, Jwu-Lai
通讯作者：
Yeh, Jwu-Lai
影响因子：
2
作者：
Liu, Shenghua;Yang, Tian;Ding, Qiang
通讯作者：
Ding, Qiang
影响因子：
3.8
作者：
Pathak, Elina;Mayeux, Philip R.
通讯作者：
Mayeux, Philip R.