利多卡因对创伤性急性肺损伤时促炎性介质基因的调控和治疗作用

The gene modulation of proinflammatory cytokinis and therapy by lidocain in the traumatic acute lung injury

目的 探讨利多卡因对创伤性急性肺损伤 (ALI)的免疫干预作用及其机制。方法 撞击兔胸部加静脉注射内毒素 ,建立创伤性ALI动物模型后立即静脉给予利多卡因 ,测定血浆和支气管肺泡灌洗液中前炎性介质的浓度。留取肺、肝、肾、心组织标本进行光镜和电镜检查以及免疫组织化学和原位杂交检测。结果 ALI动物血浆和支气管肺泡灌洗液中前炎性介质浓度升高 ,与创伤前比较 ,血浆中肿瘤坏死因子 α(TNFα)和白细胞介素 (IL) 1β的峰值明显升高 [(0 .96± 0 .2 8) μg/L和(0 .90± 0 .2 5 ) μg/L ,创伤前为 (0 .18± 0 .10 ) μg/L和 (0 .10± 0 .0 6 ) μg/L ,P <0 .0 1]。利多卡因能够改善呼吸状况、血气和器官的病理改变 ,降低前炎性介质浓度 ,与模型组比较 ,血浆中TNFα和IL 1β的峰值较低 [分别为 (0 .47± 0 .14) μg/L、(0 .30± 0 .2 1) μg/L],其基因表达的细胞种类和数量明显减少。结论 利多卡因可以抑制前炎性介质的合成和分泌基因表达下调 ,从而对创伤性ALI起防治作用。

Objective To investigate the immuno-intervention effects of lidocaine and their mechanism in traumatic acute lung injury (ALI). Methods After animal model of traumatic ALI was established by impacting on the rabbit chest and injecting endotoxin intravenously,lidocaine was immediately given intravenously. The changes of levels of proinflammatory mediators in plasma and bronchoalveolar lavage fluid (BALF) were determined. The samples of lung, liver, kidney and myocardium were taken to undergo the examination under optical and electron microscopes and immunohistochemical staining and in situ hybridization test.Results In ALI animals, there were high levels of proinflammatroy mediators in plasma and BALF. In comparison with pretrauma,the peak value of tuomr necrosis factor-α (TNFα) and interlukin (IL)-1β in plasma changed with most significant difference[(0.18±0.10) μg/L and (0.10±0.06) μg/L vs (0.90±0.25) μg/L,,respectively].Lidocaine improved respiratory condition, blood gas and pathologic changes of organs, and decreased proinflammatory mediator levels. In comparison with model group, the peak value of TNFα and IL-1β in plasma was lower [(0.47±0.14) μg/L and (0.30±0.21) μg/L, respectively]. The kinds and numbers of cell of proinflammatory mediator gene expression were significantly reduced. Conclusion Lidocaine could lessen synthesis and release of proinflammatory mediators and down-regulate gene expression, so to protect and treat traumatic ALI.