急性肺损伤中AQP3在NLRP3炎症小体介导的肺巨噬细胞焦亡中的作用

急性肺损伤(ALI)及其严重阶段的急性呼吸窘迫综合征发病机制复杂、死亡率高，是现代呼吸和危重医学的一大难题。肺泡巨噬细胞（AM）发生焦亡是ALI发病的重要机制之一，但潜在的分子机制不清楚。钾离子外流使NLRP3炎症小体激活，NLRP3炎症小体促使IL-1β和IL-18成熟并释放，它也可以在细胞膜上形成微小孔道，使细胞外水内流，造成细胞溶解性死亡，即细胞焦亡。水通道蛋白3（AQP3）通过增强细胞迁移，调解水电解质平衡来维持AM的免疫功能。课题组考虑：1.AQP3是否参与水分子内流引起的AM焦亡过程？2.AQP3通过改变胞内离子梯度是否影响NLRP3炎症小体激活？本课题使用基因敲除动物模型和AQP3基因沉默细胞实验，加以炎症刺激后，检测NLRP3相关炎性因子表达，观察焦亡发生，进一步明确AQP3与AM焦亡间相关性，ALI的诊治提供新的靶点。

Acute lung injury (ALI) and its severe stage of acute respiratory distress syndrome (ARDS) are difficult problems in modern respiratory and critical medicine due to their complex pathogenesis and high mortality.The NOD-like receptor pyrin domain related protein 3 (NLRP3) inflammatory body is stimulated by a variety of pathogen-associated molecules, and the activated caspase-1 promotes the maturation and release of IL-1β and IL-18, it can also promote the formation of fine pores in the cell membrane, the cell external aqueous stream, resulting in the death of AM was dissolved (pyroptosis), i.e. coke cell death, is one of ALI / ARDS important mechanism of pathogenesis, but the molecular mechanisms underlying unknown. Research has shown that Aquaporin 3 (AQP3) maintains the immune function of AM by enhancing cell migration and mediating electrolyte balance. At present, there is no research report on AQP3 and AM pyrolysis. The research group considered: 1. As a water molecular channel, does AQP3 participate in the AM coke death process caused by water intramolayer flow? 2. Does AQP3 affect the activation process of NLRP3 inflammids by changing the intracellular ion gradient or energy metabolism? In this study, gene knockout animal model and AQP3 gene silencing cell experiment were used to detect the expression of nlrp3-related inflammatory factors and observe the occurrence of pyroptosis after inflammatory stimulation, so as to further clarify the correlation between AQP3 and AM pyroptosis, and provide a new target for the diagnosis and treatment of lung inflammation.