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1、Toll样受体4在急性肺损伤中的作用?692?中华急诊医学杂志2006年8月第l5卷第8期ChinJEmergMed,Augest2006,Vo1.15,No.8Toll样受体4在急性肺损伤中的作用张进祥王慧徐建波蒋春舫吴河水基础研究?【摘要】目的观察Toll样受体4(toll—likereceptor4,TLR4)基因突变型小鼠与野生型小鼠内毒素攻击致急性肺损伤(acutelunginjury,Au)的差异,分析TLR4在Au中的作用.方法采用TLR4基因突变小鼠(C3H/HeJ品系,TLR4.)及野生型小鼠(CBA品系,TLR4),用内毒素攻击复制
2、小鼠Au模型,用显微病理及肺干湿重比(W/D)分析肺损伤程度,检测肺组织髓过氧化物酶(MPO)水平,探讨损伤差异的可能机制.结果用l,5mg?kgLPS溶液经尾静脉注射复制Au模型,结果示TLR4突变小鼠肺组织大体及显微病理损伤较野生型小鼠减轻,同时肺组织水肿(W/D)亦较野生小鼠减轻,尤其是在大剂量(5mg?)时,差异有显着性[(4,08±0.1).(4,55±0,2),a=10,t=12,71,P<0.01].突变小鼠肺组织PMN浸润水平较野生型低[MPO:lmg?kg组,(2O.73±4.58),(39.97±3,66),a=10,t=13
3、,43,P<0,01];5mg?kg组,[(24,0±3,94),(48,5±4,07),a=10,t=15.33,P<0.01],且两者均较假手术组高.结论TLR4可能通过介导中性粒细胞肺内聚集而导致Au的发生发展.【关键词】急性肺损伤;内毒素;Toll样受体4EffectsofToll-likereceptor4inHpopolysaccharideJianbo.JIANGChunfang,uHeshui,DepartmentUniversityofScienceandTechnology,Wuhan430022,inducedacut
4、elunginjuryZHANGJinxiang,WANGHui,XUofEmergencySurgery,UnionHospitalAffiliatedtoHuazhongChina【Abstract】ObjectiveToobservethedifferenceoflunginjurybetweentoll—likereceptor4(TLR4)mutantmiceandwildtypemiceinamodeloflipopolysaeeharide(LtX5)inducedacutelunginjury(Au),discusstheroleofT
5、LR4inAU.MethodsDifferentdosesofLtX5solution(1,5mg'kg)wereinjectedinveintailtoreproduceAUmodelinbothTLR4mutant(TLR4一)andwildtype(WT,TLR4")mice,Lungtissueswerecollectedforgrossandmierographichistologicalinjuryanalysisandforassessmentoflungedema.Meanwhile,thelevelsofmyeloperoxidase
6、(MPO)inlungtissuesinbothstrainswereassessedtoevaluatetheextentofpolymorphologiealneutrophils(PMN)infiltration.ResultsThegrossandmierographieinjuryoflungwasmilderinTLR4mutantmicethanthatinwildtypemice.Theextentoflungedema(W/D)wasalsoreducedcomparedwithwildtypemice,especiallyin5mg
7、.kggroup【(4.08±0.1).(4,55±0.2),a=10,t=12,71,P<0,01J,WithhighdosageofLtX5,thevalueofW/Dinbothmicestrainswashigherthanthatinshamoperationgroup(P<0.O1).TheextentofPMNinfiltrationinlungtissuesinTLR4mutantmicewasreducedcomparedwithwildtypemice.Buttheywerehigherthanshamoperatedm
8、ice(P<0.01).ConclusionTLR4Mayinvolveinthedev
