牵张离子通道通过miRNA-146a/NF-κB通路介导呼吸机相关性肺损伤的实验研究

Experimental study of stretch-activated channel contributing to ventilator-induced lung injury via miRNA-146a NF-κB passway

目的探析呼吸机相关性肺损伤(VILI)的发生机制,为防治VILI提供新的理论依据.方法以自主呼吸大鼠为对照组(S组),大潮气量机械通气大鼠为实验组(V组),以牵张离子通道(SAC)阻滞剂大鼠作为干预措施组(V+B组),每组各12只;机械通气后比较大鼠肺组织结构和功能、miRNA-146a、NF-κBP65、炎症因子(TNF-α、IL-6)表达有无不同.结果机械通气后大鼠肺组织结构破坏明显,氧合功能明显减低,肺组织miRNA-146a表达明显下调,NF-κB P65表达上调,肺部和全身炎症因子浓度增加.相比V组大鼠,V+B组大鼠上述病变程度明显减轻,肺组织miRNA-146a表达下调减缓,NF-κB P65表达上调程度减轻,肺部和全身炎症因子浓度增加幅度减少.结论SAC可能通过miRNA-146a/NF-κB途径介导VILI发生,有望成为防治VILI的新靶点.

Ojective To explore the mechanism of ventilator-induced lung injury(VILL)and to provide some evidences for the prophylaxis and the treatment of VILI Methods The mice were divided into three groups:spontaneous inspiration(group S),high tidal volume ventilation(group V),and high tidal volume ventilation with stretch-activated channels(SAC)blocker(group V+B)with each group 12 mice.Lung morphology and function,miRNA-146a expression,NF-κB P65 expres-sion and inflammatory factors(TNF-a,IL-6)concentration in the serum and lung were evaluated in the setting of mechanical ventilation.Results Serious lesion in the lung with an obviously impaired oxygenation were observed in the mice that received high tidal volume ventilation.The expression of miRNA-146a significantly reduced,and the NF-κB P65 increased on the contra-ry.Serum and pulmonary inflammatory level elevated after ventilation.Compared with group V,morphology abnormity and ox-ygenation dysfunction relieved in the mice in the group V+B.Higher miRNA-146a level,lower NF-rB P65 expression and lower local and systemic inflammatory levels were observed in the mice of group V+B.Conclusion SAC contributes to VILI through the miRNA-146a/NF-κB passway and is expected to be a novel target for the prophylaxis and the treatment of VILI.