江苏大学学报（医学版）
江囌大學學報（醫學版）
강소대학학보（의학판）
JOURNAL OF JIANGSU UNIVERSITY (MEDICINE EDITION)
2008年
5期
369-377
,共9页
孙炳伟%陈曦%Kazuhiro Katada%Richard F Potter%Gediminas Cepinskas
孫炳偉%陳晞%Kazuhiro Katada%Richard F Potter%Gediminas Cepinskas
손병위%진희%Kazuhiro Katada%Richard F Potter%Gediminas Cepinskas
一氧化碳%盲肠结扎及穿孔%炎症反应%核因子kB
一氧化碳%盲腸結扎及穿孔%炎癥反應%覈因子kB
일양화탄%맹장결찰급천공%염증반응%핵인자kB
carbon monoxide%cecal ligation and puncture%inflammation%nuclear factor kappa B
目的:探讨外源性一氧化碳释放分子对脓毒症炎症反应的抑制作用及可能的机制.方法:应用盲肠结扎及穿孔脓毒症小鼠模型,使用外源性一氧化碳释放分子(CORM-2,8 mg/kg体质量,尾静脉注射)进行干预.检测肝、肺脏髓过氧化物酶(MPO)活性.应用内毒素(LPS,10G/ml)刺激的人脐静脉内皮细胞炎症模型,使用外源性一氧化碳释放分子(CORM-2,10-100 mol/L)进行干预.检测核因子kB(NF-kB)活性,内皮细胞黏附分子的表达,氧化产物、NO产物以及多形核白细胞对内皮细胞的黏附作用.结果:盲肠结扎及穿孔脓毒症小鼠模型使用外源性一氧化碳释放分子干预后肝、肺组织MPO活性明显下降.CORM-2抑制了LPS刺激导致的NF-kB活性上调.同时,NO产物下降,内皮细胞ICAM-1的表达抑制,白细胞对内皮细胞的黏附作用明显抑制.结论:外源性一氧化碳释放分子通过抑制NF-KB活性,抑制ICAM-1蛋白和NO的表达,抑制白细胞对内皮细胞的黏附作用,进而有效抑制脓毒症炎症反应.
目的:探討外源性一氧化碳釋放分子對膿毒癥炎癥反應的抑製作用及可能的機製.方法:應用盲腸結扎及穿孔膿毒癥小鼠模型,使用外源性一氧化碳釋放分子(CORM-2,8 mg/kg體質量,尾靜脈註射)進行榦預.檢測肝、肺髒髓過氧化物酶(MPO)活性.應用內毒素(LPS,10G/ml)刺激的人臍靜脈內皮細胞炎癥模型,使用外源性一氧化碳釋放分子(CORM-2,10-100 mol/L)進行榦預.檢測覈因子kB(NF-kB)活性,內皮細胞黏附分子的錶達,氧化產物、NO產物以及多形覈白細胞對內皮細胞的黏附作用.結果:盲腸結扎及穿孔膿毒癥小鼠模型使用外源性一氧化碳釋放分子榦預後肝、肺組織MPO活性明顯下降.CORM-2抑製瞭LPS刺激導緻的NF-kB活性上調.同時,NO產物下降,內皮細胞ICAM-1的錶達抑製,白細胞對內皮細胞的黏附作用明顯抑製.結論:外源性一氧化碳釋放分子通過抑製NF-KB活性,抑製ICAM-1蛋白和NO的錶達,抑製白細胞對內皮細胞的黏附作用,進而有效抑製膿毒癥炎癥反應.
목적:탐토외원성일양화탄석방분자대농독증염증반응적억제작용급가능적궤제.방법:응용맹장결찰급천공농독증소서모형,사용외원성일양화탄석방분자(CORM-2,8 mg/kg체질량,미정맥주사)진행간예.검측간、폐장수과양화물매(MPO)활성.응용내독소(LPS,10G/ml)자격적인제정맥내피세포염증모형,사용외원성일양화탄석방분자(CORM-2,10-100 mol/L)진행간예.검측핵인자kB(NF-kB)활성,내피세포점부분자적표체,양화산물、NO산물이급다형핵백세포대내피세포적점부작용.결과:맹장결찰급천공농독증소서모형사용외원성일양화탄석방분자간예후간、폐조직MPO활성명현하강.CORM-2억제료LPS자격도치적NF-kB활성상조.동시,NO산물하강,내피세포ICAM-1적표체억제,백세포대내피세포적점부작용명현억제.결론:외원성일양화탄석방분자통과억제NF-KB활성,억제ICAM-1단백화NO적표체,억제백세포대내피세포적점부작용,진이유효억제농독증염증반응.
Objective:To investigate the effects and potential mechanisms of tricarbonyldichlororuthenium(Ⅲ) dimmer(CORM-2)-liberated CO on anti-inflammatory response in sepsis.Methods:Sepsis in mice was induced by cecal ligation and perforation (CLP;24h).CORM-2 (8mg/kg;i.V.) was administrated immediately after induction of CLP.PMN accumulation (MPO assay) was assessed in mice lung and liver.In in vitro experiments human umbilical vein endothelial cells(HUVEC) were stimulated with LPS(10g/ml for 4 h in the presence or absence of CORM-2(10-100 mol/L).Subsequendy,activation of NF-kB,an inflammation-relevant transcription factor,along with the expression levels of ICAM-1,ROS,NO production and PMN adhesion to HUVEC were assessed.Results:Treatment of septic mice with CORM-2 attenuated PMN accumulation in the lung and liver.In parallel.CORM-2 prevented activation of NF-kB(EMSA) in LPS-stimulated HUVEC.This was accompanied by a decrease in ROS and NO production.expression of ICAM-1 and subsequent PMN adhesion tO HUVEC.Conclusion:CORM-released CO attenuated inflammatory responses by interfering with NF-kB activation and therefore decreased the expression of ICAM-l and NO production,suppressed endothelial cell pro-adhesive phenotype.
