百草枯（PQ）中毒引起肺损伤是造成患者死亡的主要原因，受到广泛关注。目前认为，PQ在肺组织的主动蓄积是持续和加剧肺损伤的关键因素，具体机制有待阐明。我们前期成功构建了对PQ抵抗的A549细胞系，其具有拮抗PQ在细胞内蓄积的特性。通过基因芯片筛查对比，发现高表达synaptotagmin1（SYT1）是减少PQ蓄积和抵抗其毒性的关键原因，提示STY1对PQ胞内蓄积有重要调控作用。已知STY1调节囊泡转运活性，而后者作为重要的生物分子转运途径被提示可能参与PQ致病的过程。因此，推测STY1可能通过调控囊泡转运活性，促进PQ跨膜排出，减轻其蓄积和肺毒性。本研究应用UPLC-MS/MS、siRNA、流式细胞术、定量PCR、western blot、共聚焦显微镜等技术，在A549细胞、ICR小鼠及临床患者多个层次阐述SYT1介导囊泡转运拮抗PQ蓄积和肺损伤的作用与机制，旨在为PQ中毒干预提供新思路。

It is widely concerned that paraquat (PQ) induced lung injury is the main cause of death for the patients with PQ poisoning. The active accumulation of PQ in the lung tissue contributes to the persistent and exacerbated lung toxicity, and the underlying molecular mechanism of PQ accumulation remains largely unknown. We successfully constructed a PQ-resistant A549 cell line, in which surprisingly existed an antagonistic effect on PQ accumulation. Based on the results of DNA microarray, we found overexpression of synaptotagmin1 (SYT1) led to the reduction of PQ accumulation and the resistance to its toxicity, suggesting that STY1 plays an important role in regulating the intracellular accumulation of PQ. It is known that STY1 regulates the vesicle transport activity which governs transport of biochemical signal molecules in the cell and seems involved in the pathogenesis of PQ poisoning. Therefore, we hypothesize that STY1 promotes the excretion of PQ by regulating the vesicle transport activity, and reduce its intracellular accumulation and lung toxicity. Here, we will explore whether SYT1 mediated vesicle transport plays a role in preventing PQ accumulation and its toxicity in A549 cells, ICR mice and clinical patients, using various methods of UPLC-MS/MS, siRNA, flow cytometry, real-time PCR, western blot, and confocal microscopy. This study will provide new insights into the PQ-induced lung injury and its treatment.