Department of Coronary Care Unit, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
Inflammation. 2016 Apr;39(2):651-62. doi: 10.1007/s10753-015-0290-2.
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-α (TNF-α) 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-κB 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.
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向组织浸润来抑制炎症反应。本研究探讨了青蒿琥酯对 HO-1 和脓毒症性肺损伤的影响。采用盲肠结扎穿孔（CLP）法诱导脓毒症性肺损伤。用青蒿琥酯（AS）（15mg/kg）预处理的小鼠，其脓毒症诱导的死亡率和肺损伤降低，肺病理变化和中性粒细胞浸润减轻。此外，AS 降低了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，抑制了肺组织中环氧化酶-2（COX-2）和诱导型一氧化氮合酶同工型（iNOS）的表达和 NF-κB 的激活。此外，AS 增强了肺组织中 NF-E2 相关因子-2（Nrf2）的激活、HO-1 的表达和酶活性。然而，HO-1 竞争性抑制剂 ZnPP IX 消除了 AS 对脓毒症性肺损伤的保护作用。因此，AS 在脓毒症性肺损伤中发挥保护作用，与 HO-1 的上调有关。这些发现为脓毒症性肺损伤提供了一种有效的治疗方法，并为 AS 的分子机制和作用提供了新的见解。
