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

作　　者：赵新云[1] 孔辉[1] 王晶晶[1] 闫晓培 刘汶睿 曾晓宁[1] 解卫平[1] 

机构地区：[1]南京医科大学第一附属医院呼吸内科,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2014年第7期898-903,共6页Journal of Nanjing Medical University(Natural Sciences)

基　　金：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)

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。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.

关 键 词：急性肺损伤 脂多糖 法舒地尔 

分 类 号：R563[医药卫生—呼吸系统]