Artesunate Protects Against Sepsis-Induced Lung Injury Via Heme Oxygenase-1 Modulation
Artesunate Protects Against Sepsis-Induced Lung Injury Via Heme Oxygenase-1 Modulation
复制标题
青蒿琥酯通过调节血红素氧合酶-1对脓毒症肺损伤的保护作用
DOI：
10.1007/s10753-015-0290-2
复制
发表时间：
2016-04-01
期刊：
影响因子：
5.1
通讯作者：
Zhao, Ming-yan
中科院分区：
文献类型：
--
作者：
Cao, Tian-hui;Jin, Song-gen;Zhao, Ming-yan
青蒿琥酯是青蒿素的衍生物，具有抗炎特性，并在脓毒症中发挥保护作用。血红素加氧酶-1（HO-1）通过减少促炎细胞因子和白细胞流入组织来抑制炎症反应。本研究探讨青蒿琥酯对HO-1和脓毒性肺损伤的影响。采用盲肠结扎穿孔（CLP）诱导脓毒性肺损伤。青蒿琥酯（AS）15 mg/kg能明显降低脓毒症小鼠的死亡率和肺损伤程度，减轻肺组织病理改变和中性粒细胞浸润。此外，AS还能降低血清和支气管肺泡灌洗液（BALF）中肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的水平，抑制肺组织中环氧合酶-2（考克斯-2）和诱导型一氧化氮合酶（iNOS）的表达及NF-κ B B的活化。此外，AS还增强了肺组织中NF-E2相关因子-2（Nrf 2）的激活以及HO-1的表达和酶活性。然而，AS对脓毒症诱导的肺损伤的保护作用被HO-1竞争性抑制剂ZnPP IX消除。因此，AS在脓毒性肺损伤中起保护作用，其机制与HO-1的上调有关。这些发现为脓毒症肺损伤的治疗提供了一种有效可行的方法，并为AS的分子机制和作用提供了新的见解。
Artesunate, a derivative of artemisinin, has anti-inflammatory properties and exerts protective roles in sepsis. Heme oxygense-1 (HO-1) inhibits the inflammatory response through reduction of proinflammatory cytokines and leukocyte influx into tissues. The present study investigated the effects of artesunate on HO-1 and septic lung injury. Cecal ligation and puncture (CLP) was employed to induce septic lung injury. Mice pretreated with artesunate (AS) (15 mg/kg) exhibited decreased sepsis-induced mortality and lung injury and alleviated lung pathological changes and neutrophil infiltration. In addition, AS lowered the levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in the serum and bronchoalveolar lavage fluid (BALF) and inhibited cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase isoform (iNOS) expression and NF-kappa B activation in lung tissue. In addition, AS enhanced NF-E2-related factor-2 (Nrf2) activation and HO-1 expression and enzymatic activity in lung tissue. However, the protective effects of AS on sepsis-induced lung injury were eliminated by ZnPP IX, an HO-1 competitive inhibitor. Therefore, AS plays protective roles in septic lung injury related to the upregulation of HO-1. These findings suggest an effective and applicable treatment to sepsis-induced lung injury and provide new insights into the molecular mechanisms and actions of AS.