国际麻醉学与复苏杂志
國際痳醉學與複囌雜誌
국제마취학여복소잡지
INTERNATIONAL JOURNAL OF ANESTHESIOLOGY AND RESUSCITATION
2012年
10期
674-677,682
,共5页
氯胺酮%乌司他丁%内毒素血症%呼吸窘迫综合征
氯胺酮%烏司他丁%內毒素血癥%呼吸窘迫綜閤徵
록알동%오사타정%내독소혈증%호흡군박종합정
Ketamine%Ulinastatin%Endotoxemia%Respiratory distress syndrome
目的 探讨氯胺酮复合乌司他丁对大鼠内毒素性急性肺损伤(acute lung injury,ALI)的影响.方法 成年雄性SD大鼠100只,体重280 g～320 g,采用计算机简单随机分组法随机分为5组(每组20只):对照组(C组)、内毒素组(L组)、氯胺酮组(K组)、乌斯他丁组(U组)、氯胺酮复合乌斯他丁组(K+U组).除C组外,其余大鼠腹腔注射0.03％脂多糖(lipopolysaccharide,LPS)1 mg/kg,注射后16 h时,由尾静脉再次注射0.1％ LPS 1.5 mg/kg,建立大鼠ALI模型.U组、K+U组分别在第2次注射LPS后经尾静脉注射乌司他丁50 000 U/kg,注射乌司他丁后即刻,K组、K+U组经尾静脉以微量泵持续输注氯胺酮10 mg·kg-1·h-1,其余组注射等容量生理盐水.于第2次注射LPS后1、2、3、4h(T1-4)时,各组取5只大鼠,抽取腹主动脉血样0.5 ml,测定氧分压(PaO2),抽取下腔静脉血样2 ml,测定血清肿瘤坏死因子(tumor necrosis factor,TNF)-α和白介素(interleukin,IL)-6浓度；放血处死大鼠,取右肺上叶组织,光镜下观察肺组织病理学结果,进行肺组织病理半定量评分及测定核因子(nuclear factor-κB,NF-κB)抑制蛋白α(inhibitor of nuclear factor κBα,IκBα)表达；取右肺中叶组织100 mg测定肺组织NF-κB活性；取右肺下叶组织,计算肺湿干重比(W/D).结果 与C组比较,L组、K组、U组和K+U组PaO2降低,血清TNF-α、IL-6浓度和肺组织NF-κB活性升高,IκBα表达降低,W/D升高(P＜0.01)；与L组比较,K组、U组和K+U组PaO2升高,血清TNF-α、IL-6浓度和肺组织NF-κB活性降低,IκBα表达升高,W/D降低,肺组织病理评分降低(P＜0.05或0.01)；与K组和U组比较,K+U组各时点PaO2升高,血清TNF-α、IL-6浓度和肺组织NF-κB活性(2.49±0.23)降低,IκBα表达(35.1±3.4)升高,W/D(4.91±0.16)降低,肺组织病理评分(7.8±0.8)降低(P＜0.05或0.01).结论 氯胺酮复合乌司他丁可减轻大鼠ALI,较两者单独应用效果显著.
目的 探討氯胺酮複閤烏司他丁對大鼠內毒素性急性肺損傷(acute lung injury,ALI)的影響.方法 成年雄性SD大鼠100隻,體重280 g～320 g,採用計算機簡單隨機分組法隨機分為5組(每組20隻):對照組(C組)、內毒素組(L組)、氯胺酮組(K組)、烏斯他丁組(U組)、氯胺酮複閤烏斯他丁組(K+U組).除C組外,其餘大鼠腹腔註射0.03％脂多糖(lipopolysaccharide,LPS)1 mg/kg,註射後16 h時,由尾靜脈再次註射0.1％ LPS 1.5 mg/kg,建立大鼠ALI模型.U組、K+U組分彆在第2次註射LPS後經尾靜脈註射烏司他丁50 000 U/kg,註射烏司他丁後即刻,K組、K+U組經尾靜脈以微量泵持續輸註氯胺酮10 mg·kg-1·h-1,其餘組註射等容量生理鹽水.于第2次註射LPS後1、2、3、4h(T1-4)時,各組取5隻大鼠,抽取腹主動脈血樣0.5 ml,測定氧分壓(PaO2),抽取下腔靜脈血樣2 ml,測定血清腫瘤壞死因子(tumor necrosis factor,TNF)-α和白介素(interleukin,IL)-6濃度；放血處死大鼠,取右肺上葉組織,光鏡下觀察肺組織病理學結果,進行肺組織病理半定量評分及測定覈因子(nuclear factor-κB,NF-κB)抑製蛋白α(inhibitor of nuclear factor κBα,IκBα)錶達；取右肺中葉組織100 mg測定肺組織NF-κB活性；取右肺下葉組織,計算肺濕榦重比(W/D).結果 與C組比較,L組、K組、U組和K+U組PaO2降低,血清TNF-α、IL-6濃度和肺組織NF-κB活性升高,IκBα錶達降低,W/D升高(P＜0.01)；與L組比較,K組、U組和K+U組PaO2升高,血清TNF-α、IL-6濃度和肺組織NF-κB活性降低,IκBα錶達升高,W/D降低,肺組織病理評分降低(P＜0.05或0.01)；與K組和U組比較,K+U組各時點PaO2升高,血清TNF-α、IL-6濃度和肺組織NF-κB活性(2.49±0.23)降低,IκBα錶達(35.1±3.4)升高,W/D(4.91±0.16)降低,肺組織病理評分(7.8±0.8)降低(P＜0.05或0.01).結論 氯胺酮複閤烏司他丁可減輕大鼠ALI,較兩者單獨應用效果顯著.
목적 탐토록알동복합오사타정대대서내독소성급성폐손상(acute lung injury,ALI)적영향.방법 성년웅성SD대서100지,체중280 g～320 g,채용계산궤간단수궤분조법수궤분위5조(매조20지):대조조(C조)、내독소조(L조)、록알동조(K조)、오사타정조(U조)、록알동복합오사타정조(K+U조).제C조외,기여대서복강주사0.03％지다당(lipopolysaccharide,LPS)1 mg/kg,주사후16 h시,유미정맥재차주사0.1％ LPS 1.5 mg/kg,건립대서ALI모형.U조、K+U조분별재제2차주사LPS후경미정맥주사오사타정50 000 U/kg,주사오사타정후즉각,K조、K+U조경미정맥이미량빙지속수주록알동10 mg·kg-1·h-1,기여조주사등용량생리염수.우제2차주사LPS후1、2、3、4h(T1-4)시,각조취5지대서,추취복주동맥혈양0.5 ml,측정양분압(PaO2),추취하강정맥혈양2 ml,측정혈청종류배사인자(tumor necrosis factor,TNF)-α화백개소(interleukin,IL)-6농도；방혈처사대서,취우폐상협조직,광경하관찰폐조직병이학결과,진행폐조직병리반정량평분급측정핵인자(nuclear factor-κB,NF-κB)억제단백α(inhibitor of nuclear factor κBα,IκBα)표체；취우폐중협조직100 mg측정폐조직NF-κB활성；취우폐하협조직,계산폐습간중비(W/D).결과 여C조비교,L조、K조、U조화K+U조PaO2강저,혈청TNF-α、IL-6농도화폐조직NF-κB활성승고,IκBα표체강저,W/D승고(P＜0.01)；여L조비교,K조、U조화K+U조PaO2승고,혈청TNF-α、IL-6농도화폐조직NF-κB활성강저,IκBα표체승고,W/D강저,폐조직병리평분강저(P＜0.05혹0.01)；여K조화U조비교,K+U조각시점PaO2승고,혈청TNF-α、IL-6농도화폐조직NF-κB활성(2.49±0.23)강저,IκBα표체(35.1±3.4)승고,W/D(4.91±0.16)강저,폐조직병리평분(7.8±0.8)강저(P＜0.05혹0.01).결론 록알동복합오사타정가감경대서ALI,교량자단독응용효과현저.
Objective To investigate the effects of ketamine combined with ulinastatin against endotoxin-induced acute lung injury (ALI) in rats Methods One hundred healthy male SD rats,weight 208 g-320 g,were randomly divided into 5 groups equally:group I normal control ( C ) ; group Ⅱ endotoxin (L) ; group Ⅲ ketamine ( K ) ; group Ⅳ ulinastatin (U) and group Ⅴ ( K+U).The animals received 2 doses of lipopolysaccharide (LPS) (intraperitoneal LPS 1 mg/kg and iv LPS 1.5 mg/kg) at 16 h interval in group Ⅱ togroupⅤ.The animals received ulinastatin 50 000 U/kg iv after second dose of LPS in group U and K+U.Ketamine was infused iv at 10 mg·kg-1·h-1 in group K and K+U.Five animals in each group were killed by exsanguination at 1,2,3 and 4 h after second LPS administration.W/D lung weight ratio,blood gases,serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 concentrations and nuclear factor-κB (NF-κB) activity and inhibitor of nuclear factor κBα (IκBα) protein expression in the lung tissue were determined. Results LPS administration significantly increased serum TNF-α and IL-6 concentration and NF-κB activity in the lung tissue and decreased IκBα protein expression in group Ⅱ as compared with control group.The LPS-induced changes were attenuated by K/U/K+U in group Ⅲ, Ⅳ and Ⅴ. Compared with group K or group U,serum TNF -αand IL-6 concentration and NF-κB activity (2.49±0.23) in the lung tissue decreased,IκBα protein expression (35.1±3.4) increased significantly,and W/D lung weight ratio (4.91±0.16) and lung pathologic score (7.8±0.8) were lower in group K+U.Conclusions Ketamine and ulinastatin have protective effects against LPS induced acute lung injury by inhibiting NF-κB activity,neutrophil activation and inflammatory responses,and are synergistic.
