严重创伤致中枢神经系统功能障碍的防治是医学领域研究的热点与难点。我们前期研究表明，小鼠腹部创伤性手术后血脑屏障（ BBB）通透性增加并诱发认知功能障碍，而显著增高的外周血循环IL-6是造成BBB通透性增加的关键因素，然而其作用于BBB的方式和分子机制尚未明确。已有研究提示水通道蛋白家族（AQP）在应激和炎症环境下可使BBB通透性增高，这是否也是外周血IL-6破坏BBB完整性并产生认知功能障碍的作用机制亟待需要被研究和证实。基于此，本研究拟采用手术创伤模型，系统观察IL-6与BBB通透性及脑水肿的关系，检测AQP家族蛋白的表达；建立体外BBB模型寻找响应IL-6的特定AQP，及其在BBB通透性调控中的作用；最后针对特定AQP构建基因编辑小鼠，体内验证AQP在创伤发生后与BBB通透性关系。本研究将为临床防治严重创伤导致的BBB通透性改变，乃至发展成为认知功能障碍提供重要的理论依据和关键技术。

The treatment and prevention of central nerves system (CNS) dysfunction leaded by severe trauma has always been a puzzle in medical science. Our latest study confirmed that severe traumatic surgery (laparotomy) impairs blood brain barrier through the elevated serum Interleukin-6 (IL-6) and finally leads to cognitive dysfunction in mice, which mechanism, however, remains largely unknown. Existing research indicated that Aquaporin (AQP) family could break the integrity of BBB and induce brain edema (BE) under stress and inflammatory environment. Whether AQP family involves BBB dysfunction which caused by peripheral IL-6 needs to be studied and proved. Based on above, we plan to set up a severe traumatic model of laparotomy, systematically screen the relationship between IL-6 and BBB and BE, and detect expression of AQP family; set up in vitro BBB model to search specific AQP which responds to IL-6 and its role in regulating BBB permeability; finally employ gene editing mice to verify the key role of specific AQP in BBB permeability and BE formation after severe trauma. This study should provide us a significant theoretical and technical basis of severe traumatic injury resulting in a compromised BBB and cognitive dysfunction.