Shikonin attenuates lipopolysaccharide-induced acute lung injury in mice
Shikonin attenuates lipopolysaccharide-induced acute lung injury in mice
复制标题
紫草素可减轻脂多糖诱导的小鼠急性肺损伤
DOI：
10.1016/j.jss.2012.10.039
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发表时间：
2013-06-15
影响因子：
2.2
通讯作者：
Zhao, Jin-Bo
中科院分区：
文献类型：
--
作者：
Bai, Guang-Zhen;Yu, Hai-Tao;Zhao, Jin-Bo
背景：紫草素是从紫草根中提取的一种天然的萘醌类色素，具有抗炎等多种药理作用。材料与方法：雄性BALB/C小鼠60只，随机分为6组(n=10)：对照组、紫草素组(50 mg/kg)、脂多糖组(LPS组)和紫草素治疗组(12.5、25、50 mg/kg)。气管内注入脂多糖(5 mg/kg)前1h灌胃紫草素或赋形剂。结果：紫草素预处理可明显减轻内毒素诱导的肺组织病理改变、肺泡出血和中性粒细胞的浸润。紫草素可显著降低肺湿重/干重比值作为肺水肿的指标。此外，紫草素还能降低肺泡灌洗液中肿瘤坏死因子α和白介素1β等促炎细胞因子的产生和总蛋白浓度。紫草素预处理还能降低肺组织髓过氧化物酶和一氧化氮的含量。此外，紫草素可显著抑制内毒素诱导的肺组织环氧合酶2和诱导型一氧化氮合酶的激活及核因子kappaB DNA结合活性。结论：紫草素对脂多糖诱导的急性肺损伤具有保护作用，其作用机制可能与其通过下调核因子kappaB的活化而抑制诱导型一氧化氮合酶和环氧合酶2的表达有关。(C)2013 Elsevier Inc.保留所有权利。
Background: Shikonin, a natural naphthoquinone pigment extracted from the root of Lithospermum erythrorhizon, has shown a variety of pharmacologic properties including anti-inflammatory effect. In the present study, we analyzed the role of shikonin in acute lung injury induced by lipopolysaccharide (LPS) in mice.Materials and methods: Sixty male BALB/C mice were randomly allocated into six groups (n = 10, each): control group, shikonin group (50 mg/kg), LPS group, and three different doses (12.5, 25, and 50 mg/kg) for shikonin-treated groups. Shikonin or vehicle was given with an intragastric administration 1 h before an intratracheal instillation of LPS (5 mg/kg). The severity of pulmonary injury was evaluated 6 h after LPS challenge.Results: Shikonin pretreatment significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. The lung wet-to-dry weight ratios, as the index of pulmonary edema, were markedly decreased by shikonin pretreatment. Moreover, shikonin decreased the productions of the proinflammatory cytokines including tumor necrosis factor alpha and interleukin 1 beta and the concentration of total proteins in the bronchoalveolar lavage fluid. Shikonin pretreatment also reduced the concentrations of myeloperoxidase and nitric oxide in lung tissues. In addition, shikonin pretreatment significantly suppressed LPS-induced activation of cyclooxygenase 2 and inducible nitric oxide synthase and the nuclear factor kappa B DNA-binding activity in lung tissues.Conclusions: This study indicates that shikonin may have a protective effect against LPS-induced acute lung injury, and the potential mechanism of this action may attribute partly to the inhibition of inducible nitric oxide synthase and cyclooxygenase 2 expression by downregulating nuclear factor kappa B activation. (C) 2013 Elsevier Inc. All rights reserved.