凝血酶大鼠脑内注射对核因子-κB活性及细胞间黏附因子-1mRNA表达的影响  

Effect of thrombin on NF-κB activity and ICAM-1 mRNA expression after intracerebral injection in rats

作　　者：关景霞[1] 孙圣刚[2] 余绍祖[1] 

机构地区：[1]武汉大学人民医院神经内科,武汉430060 [2]华中科技大学同济医学院附属协和医院神经内科,武汉430022

出　　处：《中华神经医学杂志》2007年第12期1240-1243,共4页Chinese Journal of Neuromedicine

摘　　要：目的探讨凝血酶(TM)大鼠脑内注射对核因子-κB(NF-κB)活性、细胞间黏附分子-1 (ICAM-1)mRNA表达及白细胞浸润的影响及其可能机制。方法TM、TM+组织蛋白酶G (CATG)、TM+N-乙酰半胱氨酸(NAC)脑内立体定向注射制作动物模型,在不同的时间点处死动物,应用EMSA技术检测NF-κB活性,RT-PCR技术检测ICAM-1 mRNA表达,测定髓过氧化物酶(MPO)活性来检测中性粒白细胞的浸润情况。结果TM脑内注射后6hNF-κB活性开始增加(P<0.05),24h时达高峰(P<0.01),然后逐渐下降。TM脑内注射后24h ICAM-1 mRNA表达开始增加(P<0.01),48h达高峰(P<0.01),然后逐渐下降。MPO活性动态变化趋势与ICAM-1 mRNA相似。TM+NAC组ICAM-1 mRNA及MPO活性与对照组比较差异均无显著性(P>0.05)。TM+CATG组NF-κB活性、ICAM-1 mRNA表达及MPO活性与对照组比较差异均无显著性(P>0.05)。结论TM通过蛋白酶激活受体-1(PAR-1)激活NF-κB,诱导ICAM-1 mRNA表达,促进白细胞浸润。Objective To explore the effect on NF-κB activity, intracellular adhesion molecule-1 （ICAM-1） mRNA expression and neutrophil infiltration after intracerebral injection of thrombin （TM） in rats and its possible mechanism. Methods TM, TM＋cathepsin G （CATG） or TM＋N-acetylcysteine （NAC） were stereotaxically injected into the right caudate nucleus of rats, which were executed at different time points. NF-κB activity was determined by the electrophoretic gel mobility shift assay （EMSA）; ICAM-1 mRNA expression was measured by reverse transcription-polymerase chain reaction （RT-PCR） technique; neutrophil infiltration was detected by myeloperoxidase （MPO） activity. Results NF-κB activity increased at 6 h after intracerebral injection ofTM （P〈0.05）, peaked at 24 h （P〈0.01） and then declined. ICAM-1 mRNA expression increased at 24 h after intracerebral injection of TM （P〈0.01 ）, peaked at 48 h （P〈0.01） and then declined. The dynamic change trend of MPO activity was similar to that ofICAM-1 mRNA. ICAM-1 mRNA expression and MPO activity of the TM＋NAC group had no significant difference compared with that of the control group （P〉0.05）. NF-κB activity, ICAM-1 mRNA expression and MPO activity of the TM＋CATG group had no significant difference compared with that of the control group （P〉0.05）. Conclusion TM activates NF-κB by protease activated receptor- 1 （PAR- 1）, which then induces ICAM- 1; expression and neutrophil infiltration.

关 键 词：凝血酶 蛋白酶激活受体-1 核因子-κB 细胞问黏附分子-1 髓过氧化 物酶 

分 类 号：R743.34[医药卫生—神经病学与精神病学]