内毒素急性肺损伤中p38MAPK、NF-κB与HO-1的关系  

Relationship of p38MAPK,NF-κB and HO-1 in LPS-induced acute lung injury in rats

作　　者：詹丽英[1] 李文澜[1] 柯伟 夏中元[1] 

机构地区：[1]武汉大学人民医院麻醉科,湖北武汉430060 [2]湖北省中山医院神经内科,湖北武汉430033

出　　处：《中国病理生理杂志》2010年第9期1790-1795,共6页Chinese Journal of Pathophysiology

摘　　要：目的:探讨内毒素急性肺损伤中丝裂原活化蛋白激酶p38(p38MAPK)、核转录因子κB(NF-κB)与血红素氧合酶-1(HO-1)的相互关系。方法:健康雄性Wistar大鼠40只,随机分为5组(n=8):对照组或生理盐水组(NS组)、内毒素组(LPS组)、血红素氧合酶-1诱导剂血晶素+内毒素组(Hemin+LPS组)、血红素氧合酶-1抑制剂锌原卟啉IX+内毒素组(ZnPPIX+LPS组)、p38MAPK抑制剂SB203580+内毒素组(SB+LPS组)。气管内滴注LPS或NS6h后检测动脉血气,右肺肺泡灌洗液(BALF)中性粒细胞比、蛋白含量,右肺上叶肺组织湿/干重比;用Westernblotting检测右肺下叶p38MAPK、NF-κB蛋白的表达;用免疫组化检测右肺中叶HO-1蛋白的表达,并进行病理学观察。结果:与NS组比较,LPS组、Hemin+LPS组、SB+LPS组、ZnPPIX+LPS组肺组织湿/干重比明显增加(P<0.05),BALF中性粒细胞比、蛋白含量显著增加(P<0.05或P<0.01),动脉血PaO2、PaCO2和HCO3-显著下降(P<0.05),肺组织p38MAPK、NF-κB蛋白表达明显增高(P<0.05),HO-1强阳性表达(P<0.01或P<0.05);与LPS组比较,Hemin+LPS组、SB+LPS组肺组织湿/干重比,肺泡灌洗液中性粒细胞比、蛋白含量明显减少(P<0.05),p38MAPK、NF-κB蛋白表达显著降低(P<0.05),HO-1的表达明显升高(P<0.05),而ZnPPIX+LPS组恰好相反;Hemin+LPS组、SB+LPS组之间动脉血PaO2、PaCO2和HCO3-,BALF中性粒细胞比、蛋白含量,肺组织湿/干重比,肺组织p38MAPK/NF-κB及HO-1蛋白的表达均无显著差异(P>0.05)。ZnPPIX+LPS组肺组织损伤最重,LPS组次之,Hemin+LPS组和SB+LPS组最轻。结论:在内毒素急性肺损伤中p38MAPK/NF-κB与HO-1相互抑制,各自独立发挥作用。AIM： To investigate the relationship of p38 mitogen-activated protein kinases （ p38MAPK） ,nuclear factor-kappa B （ NF-κB） and heme oxygenase-1 （ HO-1） in acute lung injury （ ALI） in rats. METHODS： Forty male Wistar rats were divided into 5 groups （ n = 8） at random： control group or normal saline group （ NS group） ,lipopolysaccharide group （ LPS group） ,Hemin （ inducer of HO-1） ＋ LPS group,ZnPPIX （ inhibitor of HO-1） ＋ LPS group and SB203580 （ inhibitor of p38MAPK） ＋ LPS group （ SB ＋ LPS group） . Six hours after endotracheal instillation of LPS or NS, the ratio of neutrophils and the protein contents in bronchoalveolar lavage fluid （ BALF） of right lung,the ratio of wet/dry weight （ W/D） of the superior lobe of right lung,and arterial blood gas analysis （ ABG） were examined. The protein levels of p38MAPK and NF-κB in the lower lobe of right lung were detected by Western blotting. The protein expression of HO1 in the middle lobe of right lung was measured by the method of immunohistochemisty. The structure of the lung was evaluated under light microscope. RESULTS： Compared with NS group,the ratio of neutrophils and protein contents in BALF,the ratio of W/D,the protein levels of HO-1,p38MAPK and NF-κB were obviously higher,and arterial oxygen pressure （ PaO2） ,partial pressure of carbon dioxide in artery （ PaCO2） and bicarbonate content （ HCO3-） were significantly lower in LPS group,Hemin ＋ LPS group,ZnPPIX ＋ LPS group and SB ＋ LPS group （ P 0. 05 or P 0. 01） . The ratio of neutrophils and proteins in BALF,the ratio of W/D,the protein levels of p38MAPK and NF-κB were significantly lower,the protein level of HO-1 was obviously higher in Hemin ＋ LPS group and SB ＋ LPS group than those in LPS group （ P 0. 05） ,while the changes of the parameters in ZnPPIX ＋ LPS group were in a contrary manner （ P 0. 05） . No significant difference of the parameters between Hemin ＋ LPS group and SB ＋ LPS group （ P 0. 05

关 键 词：急性肺损伤 p38有丝分裂素激活蛋白激酶 NF-ΚB 血红素氧合酶-1 

分 类 号：R[医药卫生]