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1、法舒地尔对脂多糖诱导的小鼠急性肺损伤的保护作用赵新云孔辉王晶晶闫晓培刘汶睿曾晓宁解卫平(南京医科大学第一附属医院呼吸内科南京210029)【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(acutelunginjury,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(10mg/kg)组、LPS+地塞米松(dexamethasone,Dex,5mg/kg)组。造模后观察不同时间点各组别生存率,6h处死小鼠收集血清、支气管
2、肺泡灌洗液(BALF)、肺组织,Elisa测定血清中TNF-α、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,其作用可能通过减轻受累肺组织炎症反应相关。【关键词】急性肺损伤,脂多糖,法舒地尔【
3、中图分类号】【文献标识码】AFasudilattenuateslipopolysaccharide-inducedacutelunginjuryinmiceZhaoXingyun,KongHui,WangJingjing,YanXiaopei,LiuWenrui,ZengXiaoning,XieWeiping(DepartmentofRespiratoryMedicine,theFirstAffiliatedHospitalofNanjingMedicalUniversity,Nanjing,Jiangsu210029,China)Correspondingauthor:XieWeip
4、ing,Email:wpxie@njmu.edu.cn【Abstract】Object:Toinvestigatetheprotectiveeffectsoffasudil,aRhokinaseinhibitor,ontheinflammationoflipopolysaccharide(LPS)-inducedmiceacutelunginjury(ALI)secondarytosepsisandit’sprobablymechanisminmice.Methods:C57BL/6micewererandomlyassignedtoControlgroup;LPSgroup;LPS+
5、fasudil(10mg/kg)group;LPS+Dexamethasone(Dex,5mg/kg)group.Mortalityratesofdifferenttimepointsofeachgroupwasassessedafterthemodelestablished.Miceweresacrificedat6hafterLPSinjection.Serum,bronchoalveolarlavagefluid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
6、临床医学研究中心(BL2012012)通讯作者(Correspondingauther):解卫平Email:wpxie@njmu.edu.cn(BALF)andlungtissueswerecollected.ElisawasperformedtoanalyzethelevelofTNF-α、IL-1βandIL-10intheserum,analyzethecellcountingandtheproteincontentinBALF,stainwithhematoxylinandeosin;testthewet-to-dry(W/D)weight;measurethecontento
7、fmyeloperoxidase(MPO)contentinlungtissue.Results:Fasudilsignificantlyimprovedthemortalityratesandprolongedthesurvivaltimeofmice,reliefedofinflammatoryinjuryandedemaoflungtissue,decreasedMPOcontent.Moreover,fasudildownregulat