紫草素对脂多糖诱导的小鼠肺损伤的保护作用
投稿时间:2017-11-20  修订日期:2018-01-08  点此下载全文
引用本文:白光振,张成生,陈鹏,张峰,张旭,雷杰.紫草素对脂多糖诱导的小鼠肺损伤的保护作用[J].医学研究杂志,2018,47(10):64-68
DOI: 10.11969/j.issn.1673-548X.2018.10.018
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作者单位E-mail
白光振 710038 西安, 空军军医大学(第四军医大学)唐都医院胸外科
014030 包头, 中国人民解放军第二九一医院外科 
bgz1982@sina.com 
张成生 014030 包头, 中国人民解放军第二九一医院外科  
陈鹏 710038 西安, 空军军医大学(第四军医大学)唐都医院胸外科  
张峰 710038 西安, 空军军医大学(第四军医大学)唐都医院肿瘤科  
张旭 014030 包头, 中国人民解放军第二九一医院外科  
雷杰 710038 西安, 空军军医大学(第四军医大学)唐都医院胸外科 leijiemd@163.com 
基金项目:内蒙古自治区自然科学基金资助项目(2017BS0818);内蒙古自治区卫生计生科研计划项目(201703261)
中文摘要:目的 研究紫草素在小鼠ALI中的作用与机制,为ALI的药物治疗提供新的思路。方法 将BALB/c小鼠分成空白对照组、紫草素组、LPS组和LPS+紫草素组,小鼠气管内滴入LPS (5mg/kg)之前1h,预先通过灌胃法给予小鼠50mg/kg剂量的紫草素或其溶剂。LPS给药6h后采集肺泡灌洗液(BALF)及肺组织,用ELISA法检测BALF中TNF-α和IL-1β的浓度,BCA法测定BALF中蛋白浓度;肺组织行病理组织切片检查,测定肺湿干重比,比色法检测组织匀浆液中MPO活性及NO浓度,Western blot法检测肺组织中诱生型一氧化氮合成酶(iNOS)的表达水平。对上述结果进行分析,研究紫草素在ALI小鼠体内的抗炎作用与机制。结果 检测BALF中TNF-α和IL-1β的浓度以及BALF中的蛋白含量发现,紫草素+LPS组的浓度较LPS组显著降低,差异有统计学意义(P<0.05)。比色法测定肺组织中MPO活性和NO浓度发现,紫草素+LPS组也明显低于LPS组,差异有统计学意义(P<0.05)。紫草素预处理组的肺湿干重比也较LPS组明显降低,差异有统计学意义(P<0.05)。此外,紫草素预处理组的肺组织病理学改变也较LPS组有所减轻,尤其体现在肺组织炎性细胞的浸润明显减少。Western blot法检测显示,紫草素+LPS组的iNOS表达量较LPS组明显下降,差异有统计学意义(P<0.05)。结论 紫草素可在病理学改变、减轻肺水肿、减少炎性因子的释放和中性粒细胞的浸润等多方面缓解ALI。这种保护作用的潜在机制可能与紫草素抑制iNOS有关。
中文关键词:紫草素  脂多糖  肺损伤  诱生型一氧化氮合成酶(iNOS)
 
Protective Effects of Shikonin on Lipopolysaccharide Induced Lung Injury in Mice
Abstract:Objective To investigate the role of shikonin in acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. Methods Forty male BALB/c mice were randomly allocated into 4 groups (n=10, each):control group, shikonin group, LPS group, and LPS+shikonin group. Shikonin (50mg/kg) or vehicle was given with an intragastric administration 1 hour before intratracheal instillation of LPS (5mg/kg). The severity of pulmonary injury was evaluated 6 hours after LPS challenge. Results Shikonin pretreatment significantly attenuated LPS-induced pulmonary histopathological changes, alveolar hemorrhage and neutrophil infiltration. The lung wet/dry weight ratios, as the index of pulmonary edema, were markedly decreased by shikonin pretreatment. Moreover, Shikonin decreased the productions of the pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β and the concentration of total proteins in the bronchoalveolar lavage fluid (BALF). Shikonin pretreatment also reduced the concentrations of myeloperoxidase (MPO) and nitric oxide (NO) in lung tissues. In addition, shikonin pretreatment significantly suppressed LPS-induced activation of inducible nitric oxide synthase (iNOS) in lung tissues. Conclusion This study provides evidence that shikonin has a protective effect against LPS-induced ALI, and the potential mechanism of this action may attribute partly to the inhibition of iNOS.
keywords:Shikonin  Lipopolysaccharide  Acute lung injury  Inducible nitric oxide synthase
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