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1 h。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、细胞粘附分子-1（ICAM-1）mRNA含量；Western blot法测定肺组织中核因子-κb（NF-κb）/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-κb/P65含量：IR组[TNF-α mRNA:(2.91±0.49)μg/L,ICAM-1 mRNA：(2.39±0.58)μg/L，NF-κb/P65：(1.97±0.17) μg/L]高于Sham组[TNF-α mRNA：(1.75±0.29)μg/L，ICAM-1 mRNA：(1.63±0.33)μg/L， NF-κb/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-κb/P65：(1.33±0.30) μg/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-κb/P65正相关，R=0.849（P<0.05），ICAM-1 mRNA与NF-κb/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。
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 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 pretrestment 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-1mRNA[Ket group:(1.78±0.28) vs IR group:(2.39±0.58) up-regulation in lung tissues. Ketamine inhibited up-regulation of NF-κb/p65[Ket group:(1.33±0.30) μg/L vs IR group:(1.97±0.17)μg/L] and NF-κb/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-κb/P65 passway.
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