JNK信号转导通路在大潮气量机械通气诱发兔肺泡巨噬细胞分泌IL-8和TNF-α中的作用

目的 评价c-Jun氨基末端激酶(JNK)在大潮气量机械通气诱发兔肺泡巨噬细胞分泌IL-8和TNF-α中的作用.方法 清洁级雄性新西兰白兔30只,体重210～260 g,随机分为3组(n=10):正常对照组(C组)不予任何刺激;机械通气组(V组)大潮气量机械通气3 d,VT 15 ml/kg,I∶E 1∶2,RR 30～40次/min,PEEP 0;SB203580干预组(S组)大潮气量机械通气3 d,同时每天机械通气时静脉注射JNK特异性抑制剂(SB203580)6 mg/kg,通气参数同V组.采用ELISA法检测支气管肺泡灌洗液中IL-8和TNF-α浓度,同时收集肺泡巨噬细胞,体外培养2 h后应用RT-PCR法检测IL-8 mRNA和TNF-α mRNA水平.结果 与C组比较,V组TNF-α、TNF-α mRNA、IL-8、IL-8 mRNA水平升高(P＜0.05).与V组比较,S组TNF-α和TNF-α mRNA水平降低(P＜0.01),IL-8和IL-8 mRNA水平差异无统计学意义(P＞0.05).结论 JNK信号转导通路在大潮气量机械通气诱发兔肺泡巨噬细胞分泌TNF-α过程中起重要作用,而不参与分泌IL-8的过程.

Role of JNK signal transduction pathway in IL-8 and TNF-α secretion from alveolar macrophages induced by mechanical ventilation with large-tidal volume in rabbits

Objective To investigate the role of c-Jun N-terminal kinase (JNK) signal transduction pathway in IL-8 and TNF-α secretion from alveolar macrophages induced by mechanical ventilation with large-tidal volume in rabbits. Methods Thirty male New Zealand white rabbits weighing 210-260 g were randomly divided into 330-40 bpm, PEEP 0), and SB203580 group (group S). The animals were anesthetized with iv pentobarbital sodium 40 mg/kg, traeheostomized and mechanically ventilated. Group C received no mechanical ventilation. The animals were mechanically ventilated for 3 days in group V. The animals were mechanically ventilated for 3 days and SB203580 (a specific JNK inhibitor) 6 mg/kg was injected via the ear vein every day during ventilation (the ventilation parameters were the same as those in group V). The animals were then sacrificed by exsanguination. The concentrations of IL-8 and TNF-α in bronchoalveolar lavage fluid (BALF) were determined by ELISA and the alveolar macrophages were collected. After the macrophages were cultured for 2 h in vitro, the expression of IL-8 mRNA and TNF-α mRNA was determined by RT-PCR. Results Compared with group C, the levels of IL-8 , TNF-α,IL-8 mRNA and TNF-α mRNA were significantly increased in group V (P＜0.05). Compared with group V, the levels of TNF-α and TNF-α mRNA were significantly decreased ( P ＜ 0.01 ), but no significant change was found in the levels of IL-8 and IL-8 mRNA in group S ( P ＞ 0.05). Conclusion JNK signal transduction pathway plays an important role in TNF-α secretion from alveolar macrophages induced by mechanical ventilation with large-tidal volume in rabbits, but is not involved the secretion of TNF-α.