长时间机械通气(PMV) 治疗的重症患者肺部常发生反复感染和持续组织损伤（呼吸机相关性肺炎，VAP），易引起肺部炎症失控，是ICU中此类患者治愈率差和死亡率高的主要原因，具体机制尚未明确。根据文献报道及我们的工作基础，推测HMGB1（一种重要的损伤相关模式分子）在肺失控性炎症中发挥重要作用。具体机制可能为，机械通气活化TGF-β，TGF-β与HMGB1相互诱生，HMGB1的持续产生放大了肺部的炎症反应并造成组织损伤，同时削弱机体对细菌的防御力引起反复感染，这可能是VAP中肺部炎症失控的主要原因。据此，本课题拟以盲肠结扎穿孔模型诱导肺损伤，在此基础上行PMV合并细菌感染，通过此肺部非可控性炎症模型，并结合临床，探讨HMGB1及其相关信号通路参与肺部炎症失控的机制。通过本项目将为阐明肺部炎症失控机制提供新的依据，为解决ICU内ALI/ARDS患者机械通气后肺部失控性炎症问题提供新的策略。

Patients suffered from ALI/ARDS are likely be receiving treatment of mechanical ventilation(MV),but prolonged mechanical ventilation(PMV) may cause lung inflammation uncontrollable,also known as nonresolving inflammation which characterized by repeated infection due and continued tissue damage.It was the main reason of the low cute rate and high motality of this kind of people in ICU,the definite mechanisms inside were unknown.Based on the relevant articles and fundamental work we have done,we suppose that HMGB1,working as a amplifying factor,may play a vital role in lung nonresolving inflammation.The underlying mechanism maybe that mechanical ventilation can activate TGF-β and HMGB1 together with TGF-βcan induce each other's generation,finally a large quantity releasing of HMGB1 can damage the tissue by amplifying the lung inflammation and cause the continued infection by impairing the ability of organism to denfense the 1`opportunistic pathogen,which directly affect the occurrence and development of lung nonresolving inflammation caused by ventilator assossiated pneumonia.Therefore,we plan to use cecal ligation and puncture model to induce the basal lung injury,then practise PMV tegether with bacterial infection,we intend to discuss how HMGB1 and its relevant signal path working on lung nonresolving inflammation via this model combined with clinical research.Our work can provide new evidence to illucidate the mechanism of lung nonresolving inflammation,moreover we can offer new strategy to resolve the issues of ALI/ARDS patients' lung nonresolving inflammation after receiving mechanical ventilation.