基于剂量的雷公藤抗小鼠免疫性炎症“效毒”关联性评价(1)
[摘要]目的:研究雷公藤水煎液发挥抗免疫炎症药效同时产生的伴随毒性作用,为其“药效-毒性”相关性研究提供实验依据。方法:建立二硝基氟苯诱导小鼠迟发型超敏反应模型,连续给予不同剂量的雷公藤水煎液5d,观察小鼠耳肿胀抑制率及其毒副作用,于末次给药后检测血中PGE2,TNF-α,IL-2,ALT,AST,PA,TBA,TBIL等生化指标水平的变化,并计算心、肝、肾、脾、肾等脏器指数。结果:连续多次给小鼠灌胃雷公藤水煎液可明显抑制DNFB致小鼠耳肿胀,其ED50及其95%可信限为0.34(0.21~0.42)g·kg-1。血中PGE2,TNF-α,IL-2含量降低,呈现一定的剂量依赖关系;小鼠血中AST,ALT,TBA,TBIL活性升高,PA含量降低。结论:雷公藤水煎液在0.59~2.34g·kg-1具有较强的抗免疫炎症作用,呈现“量-效”关系,同时可对小鼠肝脏产生一定的毒副作用,高剂量(2.34~4.68g·kg-1)可引起实质性肝损伤,肝功能指标呈现剂量依赖性。因此,雷公藤的“功效-毒性”具有一定的依赖于剂量的相关性,为今后临床预防药品不良反应的预警方案提供参考,确保雷公藤临床用药安全。
, 百拇医药
[关键词]雷公藤;剂量;免疫炎症;功效;毒性
Evaluationondosage-basedefficacy-toxicitycorrelationofTripterygium
wilfordiiagainstimmuneinflammationinmice
ZHAOQing-hua1,2,LIXiao-yu/1,FENGQun/1,SUNRong1*
(1.ShandongAcademyofChineseMedicine,Ji′nan250014,China;2.ShandongUniversityofTraditionalChineseMedicine,Ji′nan250355,China;3.TianjinUniversityofTraditionalChineseMedicine,Tianjin300193,China)
, http://www.100md.com
[Abstract]Objective:Tostudytheanti-immuneinflammationefficacyandtoxicityofTripterygiumwilfordiidecoction,inordertoprovideexperimentalbasisforstudiesonits″efficacy-toxicity″correlation.Method:Thedelayedhypersensitivitymodelwasestablishedbydinitrofluorobenzeneinmice.DifferentdosesofT.wilfordiidecoctionwasadministeredfor5consecutivedays.Theearswellinginhibitionratioandthetoxicactionwereobserved.Afterthefinaladministration,thebiochemicalindexesofPGE2,TNF-α,IL-2,ALT,AST,PA,TBA,TBILinserumweredetected,andthevisceralindexesofheart,liver,spleenandkidneyweremeasured.Result:TheDNFB-inducedearswellingcouldbenotablyinhibitedbymultipleoraladministrationofT.wilfordiidecoction,withtheED50andits95%confidencelimitof0.34(0.21-0.42)g·kg-1.ThecontentsofPGE2,TNF-α,IL-2inserumdecreasedinadose-dependentmanner.TheactivitiesofserumAST,ALT,TBA,TBILandthePAcontentreduced.Conclusion:T.wilfordiidecoctionshowsasignificantanti-immuneinflammationefficacywithinthedosagerangebetween0.59and2.34g·kg-1inadose-dependentmanner.Withacertainhepatotoxicity,highdose(2.34-4.68g·kg-1)ofT.wilfordiidecoctioncancausesubstantialliverinjury,withadosedependenceinliverfunctionindex.Therefore,theefficacyandtoxicityofT.wilfordiiisdosedependent,whichprovidesreferenceforpreventingadversedrugreactionsinclinicanddevelopingearly-warningschemesandensuretheclinicalmedicationsafetyofT.wilfordii.
[Keywords]Tripterygiumwilfordii;dose;immuneinflammation;efficacy;toxicity, http://www.100md.com(赵庆华 李晓宇 冯群 孙蓉)
, 百拇医药
[关键词]雷公藤;剂量;免疫炎症;功效;毒性
Evaluationondosage-basedefficacy-toxicitycorrelationofTripterygium
wilfordiiagainstimmuneinflammationinmice
ZHAOQing-hua1,2,LIXiao-yu/1,FENGQun/1,SUNRong1*
(1.ShandongAcademyofChineseMedicine,Ji′nan250014,China;2.ShandongUniversityofTraditionalChineseMedicine,Ji′nan250355,China;3.TianjinUniversityofTraditionalChineseMedicine,Tianjin300193,China)
, http://www.100md.com
[Abstract]Objective:Tostudytheanti-immuneinflammationefficacyandtoxicityofTripterygiumwilfordiidecoction,inordertoprovideexperimentalbasisforstudiesonits″efficacy-toxicity″correlation.Method:Thedelayedhypersensitivitymodelwasestablishedbydinitrofluorobenzeneinmice.DifferentdosesofT.wilfordiidecoctionwasadministeredfor5consecutivedays.Theearswellinginhibitionratioandthetoxicactionwereobserved.Afterthefinaladministration,thebiochemicalindexesofPGE2,TNF-α,IL-2,ALT,AST,PA,TBA,TBILinserumweredetected,andthevisceralindexesofheart,liver,spleenandkidneyweremeasured.Result:TheDNFB-inducedearswellingcouldbenotablyinhibitedbymultipleoraladministrationofT.wilfordiidecoction,withtheED50andits95%confidencelimitof0.34(0.21-0.42)g·kg-1.ThecontentsofPGE2,TNF-α,IL-2inserumdecreasedinadose-dependentmanner.TheactivitiesofserumAST,ALT,TBA,TBILandthePAcontentreduced.Conclusion:T.wilfordiidecoctionshowsasignificantanti-immuneinflammationefficacywithinthedosagerangebetween0.59and2.34g·kg-1inadose-dependentmanner.Withacertainhepatotoxicity,highdose(2.34-4.68g·kg-1)ofT.wilfordiidecoctioncancausesubstantialliverinjury,withadosedependenceinliverfunctionindex.Therefore,theefficacyandtoxicityofT.wilfordiiisdosedependent,whichprovidesreferenceforpreventingadversedrugreactionsinclinicanddevelopingearly-warningschemesandensuretheclinicalmedicationsafetyofT.wilfordii.
[Keywords]Tripterygiumwilfordii;dose;immuneinflammation;efficacy;toxicity, http://www.100md.com(赵庆华 李晓宇 冯群 孙蓉)