环氧合酶-2和核因子-κB在脓毒症大鼠肝损伤中的表达  

Express of cyclooxygenase-2 and NF-κB for hepatocellular injury in rats with sepsis

作　　者：李斌[1] 刘丽平[1] 郭鸿[1] 李汛[1] 

机构地区：[1]兰州大学第一医院重症医学科,甘肃兰州730000

出　　处：《中国医药导报》2014年第8期14-18,共5页China Medical Herald

摘　　要：目的 探讨环氧合酶2（COX-2）和核因子-κB（NF-κB）在脓毒症大鼠的肝组织炎性反应中的表达及其相互关系.方法 随机选择54只200～220 g成年Wistar大鼠分为3组,假手术A组（实验开始前2h腹腔内注射生理盐水,麻醉后行开腹手术,不做模型诱导,n=6）;脓毒症模型B组[实验开始前2h腹腔内注射生理盐水,麻醉后盲肠结扎穿孔（cecal ligation and puncture,CLP）建立腹腔感染模型,n=24]; NS398干预C组（CLP建立腹腔感染模型,实验开始前2h腹腔内注射NS398 10 mg/kg,n=24）.以CLP法建立动物模型,逆转录聚合酶链反应（RT-PCR）法检测COX-2 mRNA在肝脏组织的表达,免疫组织化学法（Elisa）测定NF-κB在肝细胞中表达,并检测肝脏功能,如谷丙转氨酶（ALT）、谷草转氨酶（AST）和肝脏大体标本及病理变化.结果 ①COX-2 mRNA在A组呈低表达（1040.82±2.77）,各时点C组较B组明显降低.②肝细胞中NF-κB在A组表达较低[3 h：（0.60±0.54）,6 h：（0.60±0.54）,12 h：（0.60±0.54）,24 h：（0.60±0.54）],脓毒症后其表达明显增高[3 h：（2.60±0.55）,6 h：（7.20±1.09）,12 h：（12.20±0.32）,24 h：（6.40±0.73）];在同一时点比较,B组低于C组[3 h：（1.60±1.89）,6 h：（6.60±0.79）,12 h：（9.20±2.68）,24 h：（4.80±1.60）]（P＜0.05）.③Pearson相关分析,COX-2 mRNA与NF-κB呈直线正相关（r=0.685,P=0.002）.④脓毒症后肝脏转氨酶明显增高[ALT：3 h：（174.00±18.73）U/L,6 h：（204.67±23.59）U/L,12 h：（311.00±44.53）U/L,24 h：（506.67±24.79）U/L;AST：3 h：（619.67 ±145.81）U/L,6 h：（594.00±34.59）U/L,12 h：（1027.66 ±136.21）U/L,24 h：（1518.33 ±139.38）U/L],NS-398干预后降低[ALT：3 h：（105.33±18.01）U/L,6 h：（157.00±32.36）U/L,12 h：（101.00±16.52）U/L,24 h：（93.33±10.41）U/L;AST：3 h：（217.00±26.21）U/L,6 h：（461.33±22.01）U/L,12h：（322.00±72.33）U/L,24 h：（268.00±98.57）U/L],C组与B组差异有统计�Objective To study the expression of cyclooxygenase 2 and NF-κB on hepatic inflammatory reaction of rats with sepsis and their interrelation.Methods 54 Wistar rats （200-220 g） were randomly divided into 3 groups.A：sham group （with saline injected into intraperitoneal 2 h before the experiment,and operation after anesthesia,no-maked model induced,n =6）; B：sepsis model group （with saline injected into intraperitoneal 2 h before the experiment,and to make sepsis model after anesthesia by using CLP,n =24）; C：NS-398 intervention group （to make sepsis model by using CLP,NS398 10 mg/kg injected into intraperitoneal 2 h before the experiment,n =24）.Animal model was established with cecum ligation perforation （CLP） method.RT-PCR were used to determine COX-2 mRNA expression in liver tissue,NF-κB of hepatocyte was detected by immunohistochemical method.At the same time,ALT,AST and liver pathological changes were detected.Results ①The expression of COX-2 mRNA were lower in group A （1040.82±2.77）,higher in group B than C at the same time.②The expression of NF-κB were lower in hepatocyte in group A [3 h：（0.60±0.54）,6 h：（0.60±0.54）,12 h：（0.60±0.54）,24 h：（0.60±0.54）],but higher after CLP [3 h：（2.60±0.55）,6 h：（7.20±1.09）,12 h：（12.20±0.32）,24 h：（6.40±0.73）],but were higher in group B than in group C [3 h：（1.60±1.89）,6 h：（6.60±0.79）,12 h：（9.20±2.68）,24 h：（4.80±1.60）] at the same time （P 〈0.05）.According to Pearson correlation analysis,it was positive correlation between cyclooxygenase-2 mRNA and NF-κB （r =0.685,P =0.042）.③Serum ALT and AST were significantly increased in B [ALT：3 h：（174.00±18.73）U/L 6 l：（204.67±2359）U/L,12 h：（311.00±44.53）U/L,24 h：（506.67±24.79）U/L; AST：3 h：（619.67±145.81）U/L,6 h：（594.00±34.59）U/L,12 h：（1027.66±136.21）U/L,24 h：（1518.33±139.38）U/L] than group C [ALT：3 h：（105.33±18.01）U/L,6 h：（157.00±32.36）U/L

关 键 词：脓毒症 COX-2 NS398 肝损伤 NF-κB 

分 类 号：R631.3[医药卫生—外科学]