利多卡因通过抑制nf-κb的活化减轻大鼠内毒素性肺损伤

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1、利多卡因通过抑制NF-κB的活化减轻大鼠内毒素性肺损伤徐州医学院附属医院麻醉科，江苏徐州221002封光刘苏王光磊刘功俭*[摘要]目的：探讨利多卡因对大鼠内毒素性肺损伤的保护作用及其机制。方法：SD大鼠随机分为1)control组(0.9%sodiumchloride);2)LPS组;3)LPS+lido1mg/kg组;4)LPS+lido2mg/kg组;5)LPS+lido4mg/kg组，其中LPS组和LPS+lido4mg/kg组又根据腹腔注射内毒素到取肺组织或收集血液标本的时间分为1、3、6、12h亚组。Western印迹检测

2、大鼠肺组织核内NF-κB和胞浆IκBα的表达，ELISA检测血清TNF-α及IL-6的水平，观察大鼠肺组织病理变化。结果：大鼠腹腔注射内毒素后，肺组织核内NF-κB的表达明显增多，血清TNF-α及IL-6的水平明显升高，胞浆IκBα表达显著减少，病理切片示肺组织结构破坏严重。应用利多卡因后，与LPS组相比，核内NF-κB的表达明显减少，胞浆中IκBα表达显著增加，血清中TNF-α及IL-6的水平也明显降低，肺组织结构的破坏有明显减轻。结论：应用利多卡因能明显抑制内毒素引起的NF-κB的活化和TNF-α、IL-6的表达。提示利多卡因的

3、肺保护作用机制可能与抑制NF-κB的活化，进而抑制炎症反应有关，而利多卡因对NF-κB活化的抑制可能与其抑制IκBα的降解有关。SummaryBackgroundandObjectives:Lidocainehasbeenreportedtoattenuatetheinflammatoryresponseinadditiontoitsanestheticactivity,butthemechanismsarepoorlyunderstood.TheobjectiveofthisstudyistodetermineifLidocain

4、epriortoendotoxemiadiminishespulmonarydysfunctionbyblockingtheNF-kappaBactivation.Methods:Ratswereassignedto:1)control(0.9%sodiumchloride);2)LPS;3)LPS+lido1mg/kg;4)LPS+lido2mg/kg;5)LPS+lido4mg/kg.LPSandLPS+lido4mg/kggroupsweresubjectedto1h、3h、6hand12htimepoint.Toinvest

5、igatetheactivationofNF-kappaB,theexpressionofNF-kappaBinthenuclearandIkappaBalphainthecytosolwereanalyzedbywesternblot.TheconcentrationofTNF-alphaandIL-6inserumwasdetectedbyELISA.ThepathologicchangesoflungwereobservedusingHEstaining.Results:Afteri.p.injectionofLPS,thee

6、xpressionofNF-kappaBinthenuclearextractswassignificantlyincreasedandIkappaBalphainthecytosolextractswasmarkedlydecreased.TheconcentrationofTNF-alphaandIL-6inserumwasincreased.Pathologicalexaminationshowedthatthenormalstructureoflungwasdestroyedbadly.HoweverLidocainerev

7、ersedaboveresults.Conclusion:LidocaineattenuatesLPS-inducedlunginjuryviamechanismsinvolvinginhibitingNF-kappaBactivationandcytokinesrelease,whichimpliesLidocainemaybeasapotentialanti-inflammatoryagentinendotoxemia.利多卡因通过抑制NF-κB的活化减轻大鼠内毒素性肺损伤[摘要]目的：探讨利多卡因对大鼠内毒素性肺损伤的保护作用

8、及其机制。方法：SD大鼠随机分为1)control组(0.9%sodiumchloride);2)LPS组;3)LPS+lido1mg/kg组;4)LPS+lido2mg/kg组;5)LPS+lido4mg/kg组，其中LPS组和LP