我们前期研究证实：机械刺激主要通过NLRP3/IL-1β及mtDNA/TLR9/MyD88通路启动炎症反应诱发VILI，同时发现，当机械刺激越大时，炎性介质如自噬小体及逃逸mtDNA反而呈下调表达，而细胞内微囊泡则呈上调表达。炎症介质是否被微囊泡吞噬呈不表达？尚未见报道。因此，我们提出假说：当炎症发生到一定程度时，细胞内形成能吞噬炎症介质的MVs，MVs被激活后介导出胞释放并在细胞间传递炎症因子致瀑布式炎症级联反应，最终导致VILI发生。为验证假说，采用荧光标记、流式细胞仪探讨MVs形成机制，采用荧光RT-PCR、Western blot等技术分析MVs成分及功能；通过基因转染、基因敲除等技术，探讨调控肺泡巨噬细胞内微囊泡形成的分子机制；通过MVs与靶细胞共培养，明确MVs的致炎作用，探讨微囊泡在细胞间传递炎症信息导致VILI的分子机制，为VILI的防治提供新靶点与新思路。

It have been convincingly shown that alveolar macrophage is the initial determinant in the VILI development. The activation and proliferation states of alveolar macrophage greatly augmented inflammation, and ultimately lead to waterfall inflammatory reaction that is the striking feature of acute lung injury. Our previous study demonstrated that alveolar macrophage initiate the inflammatory reaction mainly via NLRP3/IL-1β and mtDNA/TLR9/MyD88 signaling pathway. But how the inflammatory signal transmit from alveolar macrophage to other target cell that eventually lead to systemic inflammatory response syndrome? Its mechanism have not yet been fully elucidated. Our previous study have shown that microvesicles increased significantly with serious lung inflammation, whereas autophagosome and mtDNA expression shew down-regulation. Whether autophagosome and mtDNA were parceled by microvesicles? So we proposed that autophagosome, mtDNA and NLRP3 were parceled by microvesicles during inflammation, microvesicles package with inflammatory cargo that shed from cell via activation of signaling pathway, and the microvesicles transmit inflammatory cargo to other target recipient cells, thus mediate production of inflammatory cytokines that greatly augmented inflammation causing waterfall inflammatory reaction, and ultimately lead to VILI. To address the hypothesis, gene knockout technology, immunofluorescence microscopy, fluorescence RT-PCR and Western blot techniques et.al were adopt to elucidated the nature of signaling pathway responsible for the formation of microvesicles, and to explore the mechanism of triggering alveolar macrophages generates microvesicles that greatly augmented inflammation ultimately lead to VILI. This study will provide a new idea for the prevention and treatment of VILI.