紧密连接（TJ）在肠黏膜屏障功能（IBF）的维护中起着关键作用。既往研究多关注TJ蛋白表达变化对其影响，近来我们研究发现TJ蛋白claudin-1/4膜定位异常可能参与了IBF损伤，但其具体机制仍不清楚。新近研究表明，分选极化因子AP-1B与网格蛋白clathrin组成的AP-1B/Clathrin蛋白复合体可能在TJ蛋白膜定位机制中扮演关键角色。因此我们推测：多种病理刺激不仅引起TJ蛋白表达变化，还通过AP-1B/Clathrin复合体，引起TJ蛋白膜定位的异常，从而影响IBF。本研究拟采用体内外IBF受损模型，通过调节（基因沉默或过表达）AP-1B、Clathrin蛋白表达，利用WB、IHC、CLSM及尤斯灌流系统等，研究AP-1B/Clathrin复合体所致的TJ蛋白膜定位异常对IBF的影响，为IBF的损伤防治提供新的研究策略及靶点。

Tight junction(TJ) play a key role in the maintance of intestinal barrier function(IBF). Most of previous studies about IBF impairment focus on the expression of TJ proteins. Recently, we have demonstrated that the .membrane localization of claudin-1/4 have changed in a model of loss of IBF, which implys that the membrane localization of TJ proteins may play an improtant role in the loss of IBF, however the mechanism is not clear. Another study has identified the expression of adaptor protein-1B(AP-1B) is reduced when IBF is impaired. AP-1B usually integrates with clathrin and clathrin is closely related to TJ proteins membrane localization.Is the IBF defects not only due to the decreased expression of TJ proteins, but also due to altered TJ protein membrane localization related to AP-1B/clathrin complex? Therefore, this study will investigate the role of altered TJ protein membrane localization in the loss of IBF both in vivo and in vitro models, by using the methods of Gene overexpression, RNA interference, western blot, immunohistochemistry, laser confocal microscopy technique and so on. Thus, this study will inaugurate a new way for the research of IBF injury mechinism and its prevention.