论文部分内容阅读
目的探讨呼吸机致肺损伤时血清中细胞因子是否增高及其机制。方法通过呼吸机诱导肺损伤的体内及体外模型,将分离的肺泡上皮细胞于体外拉长,利用基因微阵列技术分析并筛选出上调的炎性细胞因子,之后给予大鼠呼吸机机械通气,留取血清标本,测量这些细胞因子在血清中是否上调。我们在体外培养的肺上皮细胞中加入外源性肿瘤坏死因子、过氧化氢或N-乙酰半胱氨酸,观察细胞因子的变化。N-乙酰半胱氨酸亦被投入大鼠呼吸机诱导肺损伤模型,观察用药后细胞因子的变化。结果转移生长因子β1(TGF-β1)和转移生长因子β2(TGF-β2)在体外拉长的肺上皮细胞中表达增加,并且在大潮气量机械通气的大鼠血清中浓度增加。肿瘤坏死因子不能改变TGF-β的表达,而过氧化氢诱导了TGF-β的上调。N-乙酰半胱氨酸减轻氧自由基损伤,不论在体内或体外试验中均阻断了过度拉长所致TGF-β在细胞及大鼠血清中的上调。结论TGF-β1和TGF-β2在通气机所致肺损伤中的表达增加并在血清中上调;TGF-β上调的机制与氧自由基损伤有关但与肿瘤坏死因子无关;N-乙酰半胱氨酸可对抗氧自由基损伤,能阻断TGF-β的上调,可能成为呼吸机相关肺损伤的一种新治疗途径。
Objective To investigate whether serum cytokines increase in ventilator-induced lung injury and its mechanism. Methods In vitro and in vivo models of lung injury were induced by ventilator. The isolated alveolar epithelial cells were lengthened in vitro. The gene expression of inflammatory cytokines was analyzed by gene microarray and then ventilated by mechanical ventilation in rats Serum samples were taken to measure whether these cytokines were up-regulated in serum. We in vitro cultured lung epithelial cells by adding exogenous tumor necrosis factor, hydrogen peroxide or N-acetylcysteine, observed changes in cytokines. N-acetyl cysteine was also injected into the rat model of lung injury induced by ventilator and observed the changes of cytokines after treatment. Results The expression of transforming growth factor β1 (TGF-β1) and transforming growth factor β2 (TGF-β2) increased in lung epithelial cells elongated in vitro and increased in the serum of mechanically ventilated rats with high tidal volume. Tumor necrosis factor can not change the expression of TGF-β, while hydrogen peroxide induced TGF-β up-regulation. N-acetylcysteine reduces oxygen free radical damage and blocks the up-regulation of TGF-β in cells and rat serum both in vivo and in vitro. Conclusion The expression of TGF-β1 and TGF-β2 in lung injury induced by ventilator increased and was up-regulated in serum. The mechanism of TGF-β up-regulation was related to oxygen free radical injury but not to tumor necrosis factor. N-acetyl cysteamine Acid can protect against oxygen free radicals and block the up-regulation of TGF-β, which may be a new therapeutic approach for ventilator-associated lung injury.