异氟醚对大鼠肺缺血再灌注损伤时NF-κB及中性粒细胞趋化因子表达的影响  

Effects of Isoflurane Administration before Ischemia on Expression of Neutrophil Chemoattractant and the DNA Binding Activity of Nuclear Factor-κB in Lung Ischemia-Reperfusion Injury in Rats

作　　者：王婷[1] 蒋豪[1] 薛张纲[1] 欧周罗[2] 

机构地区：[1]复旦大学附属中山医院麻醉科,上海200032 [2]复旦大学附属中山医院上海医学院生物化学与分子生物学系,上海200032

出　　处：《复旦学报（医学版）》2005年第4期394-400,共7页Fudan University Journal of Medical Sciences

摘　　要：目的探讨异氟醚对大鼠肺缺血再灌注损伤下核因子-κB(NF-κB)结合活性及细胞因子诱导的中性粒细胞趋化物(CINC)基因表达的影响。方法建立在体大鼠肺缺血再灌注模型。SD雄性大鼠120只,随机分成4组(n=30):手术对照组(C组),缺血再灌注组(IR组),异氟醚-缺血再灌注组(ISO-IR组)和异氟醚组(ISO-C组)。分别在缺血45min、再灌注30、60、120min处死大鼠,行动脉血气分析,测定肺组织湿干比(W/D)、髓过氧化物酶(MPO)活性、NF-κB结合活性和肺组织CINCmRNA的表达、支气管肺泡灌洗液(BALF)中白细胞计数、沉渣白细胞分类和总蛋白(TP)的含量及肺组织病理学检查。结果①再灌注后IR组和ISO-IR组的W/D值、MPO活性、NF-κB结合活性和CINCmRNA的表达均高于C组(P<0.05),而再灌注60min后ISO-IR组的以上各指标较IR组均有明显降低(P<0.05);②IR组BALF中中性粒细胞(PMN)所占的百分比较C组明显升高(P<0.05),而ISO-IR组的升高并不显著,且较IR组明显降低;③IR组和ISO-IR组BALF中TP含量均较C组升高明显(P<0.05),但ISO-IR组又明显低于IR组(P<0.05);④ISO-IR组肺组织病理学变化较IR组明显减轻。结论异氟醚的应用可以减轻肺缺血再灌注损伤,作用机制可能与其抑制NF-κB的活化,降低肺组织CINCmRNA的表达上调,减少肺内PMN的浸润密切相关。Purpose To investigate the effects of isoflurane administration before ischemia on the gene expression of cytokine-induced neutrophil chemoattractant (CINC) and the DNA binding activity of nuclear factor-κB (NF-κB) in lung ischemia-reperfusion injury in rats. Methods The rat ischemia model with occlusion of left pulmonary hilum for 45 min was used in this experiment.One hundred and twenty male Sprague-Dawley rats were randomly divided into four groups.Group C (n=30):continuous perfusion wi-thout ischemia;group IR (n=30):interruption of perfusion and ventilation for 45 min,followed by reperfusion;group ISO-IR (n=30):one MAC isoflurane inhalation for 30 min before ischemia,followed by ischemia-reperfusion;group ISO-C (n=30):one minimal alveolar concentration(MAC) isoflurane inhalation for 30 min,followed by continuous perfusion.The changes of arterial blood gas analysis,the lung wet-to-dry weight ratio (W/D),myeloperoxidase (MPO) of lung,the expression of CINC mRNA and the DNA binding activity of NF-κB were studied at 45 min after pulmonary ischemia and 30,60,120 min of reperfusion.The cell counts,percentage of PMN and total protein (TP) content in left bronchoalveolar lavage fluid (BALF) was performed at 120 min of reperfusion.MAP was continuously monitored. Results During reperfusion,the lung W/D,MPO activity,expression of CINC mRNA and the DNA binding activity of NF-κB in IR and ISO-IR groups increased progressively and was evidently higher than that in C and ISO-C groups (P< 0.05);but compared with IR group,preadministration of isoflurane could inhibit the increase of the indexes above-mentioned after 60 min of reperfusion (P<0.05).The percentage of PMN in BALF of IR group was obviously increased compared with the other groups at 120 min of reperfusion (P<0.05).IR significantly increased the content of TP in BALF of IR and ISO-IR groups,but the degree of increase in TP content of ISO-IR group was decreased markedly compared with IR group (P<0.05).Histological examination showed that the degree of injury in

关 键 词：肺缺血再灌注损伤 中性粒细胞趋化因子 异氟醚 核因子-κB(NF-κB) 支气管肺泡灌洗液 缺血再灌注模型 组织病理学检查 细胞因子诱导 结合活性 SD雄性大鼠 动脉血气分析 髓过氧化物酶 CINC mRNA BALF 白细胞计数 白细胞分类 

分 类 号：R563[医药卫生—呼吸系统] R758.630.2[医药卫生—内科学]