CAJ | 학술논문

目的观察10 mg/kg氯胺酮对于大鼠全肝缺血/再灌注诱发的急性肺损伤保护作用及其机制.方法 30只9～10周龄雌性SD大鼠以区组随机法随机分为3组(每组10只),假手术组(Sham组),全肝缺血/再灌注组(IR组)以pringle's法阻断门静脉和肝动脉30 min后再灌注1h.全肝缺血/再灌注氯胺酮预处理组(Ket组),以10 mg/kg氯胺酮于全肝血流阻断前20 min经尾静脉注射预处理.测定各组肺组织干湿重比值(W/D比值)；血清中天冬氨酸氨基转移酶(AST)、血清丙氨酸氨基转移酶(ALT)含量；逆转录/实时聚合酶链式反应( RT-PCR)法测定肺组织中血清肿瘤坏死因子-α(TNF-α)mRNA、细胞间黏附分子-1( ICAM-1 )mRNA含量；Western blot法测定肺组织中核因子-kb( NF-kJ )/P65含量；各组肺组织HE染色后病理评分.结果血清AST、ALT含量:IR组[AST:(91±25)U/ml,ALT:(67.0±19.4) U/ml]和Ket组[AST:(85±12) U/ml,ALT:(51.3±9.9) U/ml]均高于Sham组[AST:(29±9) U/ml,ALT:(7.8±2.7) U/ml] (P＜0.05).血清TNF-α、ICAM-1含量:IR组[TNF.α:(23.1±4.8) μg/L,ICAM-1:(34±9)μg/L]和Ket组[TNF-α:(19.1+5.8)μg/L,ICAM-1:(41±7) μg/L]均高于Sham组[TNF-α:(8.7±2.4) μg/L,ICAM-1:(13±5)μg/L](P＜0.05).而Ket组和IR组之间无统计学差异(P＞0.05).W/D比值:IR组(6.9±1.7)和Ket组(5.1±1.1)高于Sham组(3.7±0.7)(P＜0.05),IR组高于Ket组(P＜0.05).肺组织中TNF-α mRNA、ICAM-1 mRNA和NF-kb/P65含量:IR组[TNF-α mRNA:(2.91±0.49)μg/L,ICAM-1 mRNA:(2.39±0.58) μg/L,NF-kb/P65:(1.97±0.17) μg/L]高于Sham组[TNF-αmRNA:(1.75±0.29) μg/L,ICAM-1 mRNA:( 1.63±0.33) μg/L,NF-kb/P65:(1.06±0.24) μg/L]和Ket组[TNF-α mRNA:(2.19±0.52) μg/L,ICAM-1 mRNA:(1.78±0.28)μg/L,NF-kb/P65:(1.33±0.30μg/L](P＜0.05).Sham组和Ket组之间无统计学差异(p＞0.05).肺组织病理评分:Sham组低于IR组和Ket组(P＜0.05),Ket组低于IR组(P＜0.05).相关性:TNF-α mRNA与NF-kb/P65正相关,R=0.849(P＜0.05),ICAM-1 mRNA与NF-kb/P65正相关,R=0.639(P＜0.05).结论 10 mg/kg氯胺酮20 min前预处理对于全肝缺血/再灌注肺损伤有保护作用. 目的觀察10 mg/kg氯胺酮對于大鼠全肝缺血/再灌註誘髮的急性肺損傷保護作用及其機製.方法 30隻9～10週齡雌性SD大鼠以區組隨機法隨機分為3組(每組10隻),假手術組(Sham組),全肝缺血/再灌註組(IR組)以pringle's法阻斷門靜脈和肝動脈30 min後再灌註1h.全肝缺血/再灌註氯胺酮預處理組(Ket組),以10 mg/kg氯胺酮于全肝血流阻斷前20 min經尾靜脈註射預處理.測定各組肺組織榦濕重比值(W/D比值)；血清中天鼕氨痠氨基轉移酶(AST)、血清丙氨痠氨基轉移酶(ALT)含量；逆轉錄/實時聚閤酶鏈式反應( RT-PCR)法測定肺組織中血清腫瘤壞死因子-α(TNF-α)mRNA、細胞間黏附分子-1( ICAM-1 )mRNA含量；Western blot法測定肺組織中覈因子-kb( NF-kJ )/P65含量；各組肺組織HE染色後病理評分.結果血清AST、ALT含量:IR組[AST:(91±25)U/ml,ALT:(67.0±19.4) U/ml]和Ket組[AST:(85±12) U/ml,ALT:(51.3±9.9) U/ml]均高于Sham組[AST:(29±9) U/ml,ALT:(7.8±2.7) U/ml] (P＜0.05).血清TNF-α、ICAM-1含量:IR組[TNF.α:(23.1±4.8) μg/L,ICAM-1:(34±9)μg/L]和Ket組[TNF-α:(19.1+5.8)μg/L,ICAM-1:(41±7) μg/L]均高于Sham組[TNF-α:(8.7±2.4) μg/L,ICAM-1:(13±5)μg/L](P＜0.05).而Ket組和IR組之間無統計學差異(P＞0.05).W/D比值:IR組(6.9±1.7)和Ket組(5.1±1.1)高于Sham組(3.7±0.7)(P＜0.05),IR組高于Ket組(P＜0.05).肺組織中TNF-α mRNA、ICAM-1 mRNA和NF-kb/P65含量:IR組[TNF-α mRNA:(2.91±0.49)μg/L,ICAM-1 mRNA:(2.39±0.58) μg/L,NF-kb/P65:(1.97±0.17) μg/L]高于Sham組[TNF-αmRNA:(1.75±0.29) μg/L,ICAM-1 mRNA:( 1.63±0.33) μg/L,NF-kb/P65:(1.06±0.24) μg/L]和Ket組[TNF-α mRNA:(2.19±0.52) μg/L,ICAM-1 mRNA:(1.78±0.28)μg/L,NF-kb/P65:(1.33±0.30μg/L](P＜0.05).Sham組和Ket組之間無統計學差異(p＞0.05).肺組織病理評分:Sham組低于IR組和Ket組(P＜0.05),Ket組低于IR組(P＜0.05).相關性:TNF-α mRNA與NF-kb/P65正相關,R=0.849(P＜0.05),ICAM-1 mRNA與NF-kb/P65正相關,R=0.639(P＜0.05).結論 10 mg/kg氯胺酮20 min前預處理對于全肝缺血/再灌註肺損傷有保護作用.
목적 관찰10 mg/kg록알동대우대서전간결혈/재관주유발적급성폐손상보호작용급기궤제.방법 30지9～10주령자성SD대서이구조수궤법수궤분위3조(매조10지),가수술조(Sham조),전간결혈/재관주조(IR조)이pringle's법조단문정맥화간동맥30 min후재관주1h.전간결혈/재관주록알동예처리조(Ket조),이10 mg/kg록알동우전간혈류조단전20 min경미정맥주사예처리.측정각조폐조직간습중비치(W/D비치)；혈청중천동안산안기전이매(AST)、혈청병안산안기전이매(ALT)함량；역전록/실시취합매련식반응( RT-PCR)법측정폐조직중혈청종류배사인자-α(TNF-α)mRNA、세포간점부분자-1( ICAM-1 )mRNA함량；Western blot법측정폐조직중핵인자-kb( NF-kJ )/P65함량；각조폐조직HE염색후병리평분.결과 혈청AST、ALT함량:IR조[AST:(91±25)U/ml,ALT:(67.0±19.4) U/ml]화Ket조[AST:(85±12) U/ml,ALT:(51.3±9.9) U/ml]균고우Sham조[AST:(29±9) U/ml,ALT:(7.8±2.7) U/ml] (P＜0.05).혈청TNF-α、ICAM-1함량:IR조[TNF.α:(23.1±4.8) μg/L,ICAM-1:(34±9)μg/L]화Ket조[TNF-α:(19.1+5.8)μg/L,ICAM-1:(41±7) μg/L]균고우Sham조[TNF-α:(8.7±2.4) μg/L,ICAM-1:(13±5)μg/L](P＜0.05).이Ket조화IR조지간무통계학차이(P＞0.05).W/D비치:IR조(6.9±1.7)화Ket조(5.1±1.1)고우Sham조(3.7±0.7)(P＜0.05),IR조고우Ket조(P＜0.05).폐조직중TNF-α mRNA、ICAM-1 mRNA화NF-kb/P65함량:IR조[TNF-α mRNA:(2.91±0.49)μg/L,ICAM-1 mRNA:(2.39±0.58) μg/L,NF-kb/P65:(1.97±0.17) μg/L]고우Sham조[TNF-αmRNA:(1.75±0.29) μg/L,ICAM-1 mRNA:( 1.63±0.33) μg/L,NF-kb/P65:(1.06±0.24) μg/L]화Ket조[TNF-α mRNA:(2.19±0.52) μg/L,ICAM-1 mRNA:(1.78±0.28)μg/L,NF-kb/P65:(1.33±0.30μg/L](P＜0.05).Sham조화Ket조지간무통계학차이(p＞0.05).폐조직병리평분:Sham조저우IR조화Ket조(P＜0.05),Ket조저우IR조(P＜0.05).상관성:TNF-α mRNA여NF-kb/P65정상관,R=0.849(P＜0.05),ICAM-1 mRNA여NF-kb/P65정상관,R=0.639(P＜0.05).결론 10 mg/kg록알동20 min전예처리대우전간결혈/재관주폐손상유보호작용.
Objective To investigate the protective effect of ketamine against the lung injury observed after total hepatic ischemia (I) followed by a period of reperfusion(R).Methods Thirty female SD rats were divided into 3 groups in random.Group sham:falsely-operated animals; Group IR:total hepatic ischemia was accomplished by clipping the portal vein and hepatic artery for 30 min and the clip was then releases followed by one hour period of reperfusion period; Group Ket:ischemia and reperfusion as above,and 10 mg/kg ketamine was pretreatment 20 min before ischemia.Results ALT,AST,TNF-α and ICAM-1 of plasmatic were higher after total hepatic ischemia-reperfusion in the Group IR[AST:(91±25) U/ml,ALT:(67.0±19.4) U/ml,TNF-α:(23.1±4.8) μg/L,ICAM-1:(34+9) μg/L] and the Group Ket [AST:(85±12) U/ml,ALT:(51.3±9.9) U/ml,TNF-α:(19.1±5.8) μg/L,ICAM-1:(41±7) μg/L]compared with the sham group.Ketamine pretreatment 10 mg/kg decreased W/D ratio and pathology score.Ketamine inhibited TNF-α mRNA [ Ket group:(2.19±0.52 ) vs IR group:( 2.91 ±0.49 ) ] and ICAM-1 mRNA [ Ket group:( 1.78±0.28 )vs IR group:(2.39±0.58)]up-regulation in lung tissues.Ketamine inhibited up-cegulation of NF-kb/p65[ Ket group:(1.33±0.30) μg/Lvs IR group:(1.97±0.17) μg/L] and NF-kb/P65 related with TNF-α mRNA and ICAM-1 mRNA.Conclusions Ketamine had protective effect on total hepatic ischemia-reperfusion induced lung injury in rats,which might be associated with the inhibition of TNF-α mRNA and ICAM-1 mRNA expression in lung tissue and NF-kb/P65 passway.