地昔帕明对小鼠内毒素急性肺损伤的影响  

Influence of desipramine on lipopolysaccharide-induced acute lung injury in mice

作　　者：王乐[1,2] 刘伟[1] 廖琳玲[1,2] 刘文礼[1] 许建平[1] 汉建忠[1] 刘惠君[1] 罗自强[1] 

机构地区：[1]中南大学湘雅医学院生理学系,湖南长沙410078 [2]邵阳医学高等专科学校,湖南邵阳422000

出　　处：《中国药理学通报》2010年第1期63-66,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30370531);湖南省重点学科建设资助项目

摘　　要：目的探讨地昔帕明(DP)对脂多糖(LPS)引起的急性肺损伤的作用并初步探讨其作用机制。方法昆明种小鼠随机分为生理盐水对照组(NS组)、地昔帕明对照组(DP组)、模型组(LPS组)及地昔帕明处理组(DP+LPS组)。腹腔注射LPS建立小鼠急性肺损伤模型。造模6h后测定肺湿/干重比值(W/D)、肺泡灌洗液(BALF)中白细胞数和蛋白含量、肺组织匀浆中髓过氧化物酶(MPO)活性和丙二醛(MDA)水平,同时用ELISA法检测肺匀浆中肿瘤坏死因子-α(TNF-α)含量。结果LPS可提高小鼠肺W/D、BALF中白细胞数和蛋白含量、肺匀浆MPO活性、MDA和TNF-α含量(P<0.01),DP处理组可有效减轻LPS所引起的上述变化(P<0.05)。结论DP对LPS导致的小鼠急性肺损伤有保护作用,其保护机制可能与抑制肺TNF-α的产生,进而减轻中性粒细胞的肺部扣押和肺组织脂质过氧化损伤的程度有关。Aim To investigate the potential role of desipramine（DP） on lipoplysaccharide（LPS）-induced acute lung injury（ALI）and the mechanism of its action. Methods Kunming mice were divided into four groups randomly： NS group （NS）,DP control group （DP）,LPS group（LPS）and DP treatment group（DP＋LPS）. The model of ALI in mice was induced by lipop-lysaccharidel（LPS,10 mg·kg^-1,ip）. Six hours after LPS challenged,the lung samples were taken for determination of lung wet-to-dry weight ratio（ W/D）,my-eloperoxidase （ MPO ） activity,and malondialdehyde （ MDA ） content. The bronchoalveolar lavage fluid （BALF） samples were analyzed for total protein concentrateion and white blood cell（WBC）count. The lev-els of tumor necrosis factor-α （ TNF-α） in lung were measured by ELISA. Results LPS could significantly increase the total protein concentration and WBC number in BALF. The lung W/D ration,MPO activity,MDA content and the levels of TNF-α in lungs all increased after ip injection of LPS. Pretreatment with DP decreased all the changes induced by the LPS. Conclusion Pretreatment with DP protects lung from LPS-induced lung injury in mice,which is,at least in part, through inhibiting the level of TNF-α and decreasing the sequestration of neutrophils and lipid peroxidation.

关 键 词：地昔帕明 内毒素 急性肺损伤 肿瘤坏子因子-α 中性粒细胞 氧自由基 

分 类 号：R-332[医药卫生] R329.24