胞质型磷脂酶A2与核因子κB在单肺通气致兔肺损伤中的相互作用

目的 探讨胞质型磷脂酶A2(C-PLA2)与核因子κB(NF-κB)间相互作用关系,阐明单肺通气上调C-PLA2表达的作用机制.方法48只健康日本大耳白兔随机均分为8组:对照组;溶剂预处理组;NF-κB抑制剂(PDTC)/溶剂预处理组;C-PLA2抑制剂(AACOCF3)/溶剂预处理组;单肺通气组;溶剂预处理+单肺通气组;NF-κB抑制剂(PDTC)/溶剂预处理+单肺通气组和C-PLA2抑制剂(AACOCF3)/溶剂预处理+单肺通气组.Western-blot和定量PCR分别用于检测肺组织C-PLA2和NF-κB蛋白及mRNA表达水平;ELISA检测肺组织花生四烯酸含量;支气管-肺泡灌洗液嗜中性粒细胞计数、肺组织髓过氧化物酶活性、肺干/湿重比值和肺组织学评分用于反映肺损伤的严重程度.结果 单纯给予溶剂未对实验动物造成明显副作用.给予AACOCF3或PDTC,但未行单肺通气的实验动物除C-PLA2或NF-κB明显下调外(P<0.05),其余指标无显著变化.单肺通气实验动物肺组织C-PLA2和NF-κB表达水平均显著上调(P<0.05),出现明显的肺损伤(P<0.05);AACOCF3或PDTC预处理均可显著降低单肺通气实验动物肺组织C-PLA2和NF-κB表达水平(P<0.05),同时肺损伤程度明显减轻(P<0.05).结论 C-PLA2和NF-κB在单肺通气致肺损伤中均发挥重要作用,二者相互调控,相互影响.

Relationship between cytoplasmic phospholipase A2 and nuclear factor-κB in one-lung ventilation-induced lung injury in rabbits

Objective To elucidate the mechanisms of up-regulated expression of cytoplasmic phospholipase A2 (C-PLA2) induced by one-lung ventilation(OLV)by investigating the interactions between nuclear factor-kappaB(NF-κB)and C-PLA2. Methods Forty-eight healthy Japanese white rabbits were randomized into control group,solvent treatment group(group S), NF-κB inhibitor(PDTC)/solvent treatment group(group PS),C-PLA2 inhibitor(AACOCF3)/solvent treatment group(group AS), OLV group (group O), solvent treatment plus OLV group (SO group), NF-κB inhibitor (PDTC)/solvent treatment plus OLV group(group PSO)and C-PLA2 inhibitor(AACOCF3)/solvent treatment plus OLV group(group ASO).ELISA was used to detect arachidonic acid (AA) content in the lung tissues, and NF-κB and C-PLA2 expressions were detected by Western blotting and quantitative PCR.Lung injuries were assessed based on the lung histological score,and the polymorphonuclear leukocyte count in the bronchial-alveolar lavage fluid,myeloperoxidase(MPO)content in the lung tissues,and lung wet/dry weight (W/D) raito were determined. Results Treatment of the rabbits with the solvent did not produce any adverse effects. OLV caused obvious lung injury in the rabbits and up-regulated the expressions of C-PLA2 and NF-κB in the lung tissues(P<0.05). In rabbits without OLV, treatment with AACOCF3 or PDTC significantly down-regulated both C-PLA2 and NF-κB expressions without affecting the other parameters. In rabbits with OLV, treatment with AACOCF3 or PDTC obviously lowered C-PLA2 and NF-κB expressions and lessened the OLV-induced lung injuries. Conclusion Both C-PLA2 and NF-κB play important roles and show interactions in OLV-induced lung injury in rabbits.