文章摘要
赵新云,孔 辉,王晶晶,闫晓培,刘汶睿,曾晓宁,解卫平.法舒地尔对脂多糖诱导的小鼠急性肺损伤的保护作用[J].南京医科大学学报,2014,(7):898~903
法舒地尔对脂多糖诱导的小鼠急性肺损伤的保护作用
Fasudil attenuates lipopolysaccharide-induced acute lung injury in mice
投稿时间:2013-10-31  
DOI:10.7655/NYDXBNS20140709
中文关键词: 急性肺损伤  脂多糖  法舒地尔
英文关键词: acute lung injury  lipopolysaccharide  fasudil
基金项目:国家自然科学基金(81273571,81001427);江苏省人事厅六大人才高峰(2008074);江苏省科技厅科技支撑计划(BE2011801);江苏省呼吸病临床医学研究中心(BL2012012)
作者单位
赵新云 南京医科大学第一附属医院呼吸内科,江苏 南京 210029 
孔 辉 南京医科大学第一附属医院呼吸内科,江苏 南京 210030 
王晶晶 南京医科大学第一附属医院呼吸内科,江苏 南京 210031 
闫晓培 南京医科大学第一附属医院呼吸内科,江苏 南京 210032 
刘汶睿 南京医科大学第一附属医院呼吸内科,江苏 南京 210033 
曾晓宁 南京医科大学第一附属医院呼吸内科,江苏 南京 210034 
解卫平 南京医科大学第一附属医院呼吸内科,江苏 南京 210035 
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中文摘要:
      目的:探讨Rho激酶抑制剂法舒地尔(fasudil)对脂多糖(lipopolysaccharide,LPS)所致小鼠败血症继发急性肺损伤(acute lung injury,ALI)的保护作用及机制?方法:C57BL/6小鼠随机分为对照(Control)组?LPS模型组?LPS+fasudil(10 mg/kg)组?LPS + 地塞米松(dexamethasone,Dex,5 mg/kg)组?造模后观察不同时间点各组生存率,6 h处死小鼠收集血清?支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)?肺组织,ELISA测定血清中肿瘤坏死因子α(TNF-α)?白细胞介素(IL)-1β?IL-10水平,检测BALF中细胞计数和蛋白浓度,HE染色观察各组肺组织病理改变,湿干重比评估肺含水量,ELISA测定肺组织中性粒细胞髓过氧化物酶(myeloperoxidase,MPO)含量?结果:fasudil可显著改善动物生存率?延长生存时间;缓解肺组织炎性损伤及肺水肿程度,降低MPO含量,下调血清中促炎细胞因子IL-1β?TNF-α水平,上调抗炎细胞因子IL-10表达?结论:fasudil可有效缓解LPS所致的小鼠ALI,其作用可能与减轻受累肺组织炎症反应相关?
英文摘要:
      Objective:To investigate the protective effects of fasudil,a Rho kinase inhibitor,on the inflammation of lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice secondary to sepsis and its probably mechanism in mice. Methods:C57BL/6 mice were randomly assigned to the control group,the LPS group,the LPS+fasudil (10 mg/kg) group and the LPS+dexamethasone (Dex,5 mg/kg) group. Mortality rates of different timing of each group was assessed after the establishment of the model. Mice were sacrificed at 6 h after LPS injection. Serum,bronchoalveolar lavage fluid (BALF) and lung tissues were collected. ELISA was performed to analyze the level of TNF-α,IL-1β and IL-10 in the serum,analyze the cell count and the protein content in BALF,stain with hematoxylin and eosin;test the wet-to-dry (W/D) weight;measure the content of myeloperoxidase (MPO) content in lung tissue by ELISA. Results:Fasudil significantly improved the mortality rates and prolonged the survival time of mice,relieved inflammatory injury and edema of lung tissue,and decreased MPO content. Moreover,fasudil down regulated the expression of TNF-α and IL-1β and up regulated IL-10 in serum. Conclusion:Fasudil effectively relieved LPS-induced ALI,which may be relevant to controlling the inflammatory response in the lungs.
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