紧密连接(TJ)在维持肠黏膜屏障功能(IBF)的稳定中具有重要作用。多种损伤因素不仅能引起TJ蛋白的表达变化，还能影响其在细胞内的转运过程，从而引起TJ的损伤及IBF的损害。然而造成TJ蛋白转运异常的调控机制尚不明确。新近研究及申请者前期工作发现，细胞极性蛋白Par-3可能参与调控肠上皮细胞TJ蛋白的膜转运；同时，Par-3可调控肌球蛋白myosin II的变化。而myosin II参与转运载体从高尔基体向细胞膜迁移这一过程。因此我们推测：多种病理刺激可引起肠道上皮Par-3的改变，进一步通过调控myosin II，干扰TJ蛋白从高尔基体向细胞膜的转运，破坏紧密连接的形成，继而影响IBF的稳定性。为此，本研究拟采用体内和体外IBF 受损模型，利用免疫荧光、过表达及RNA干扰等技术，阐明Par-3通过myosin II调控TJ蛋白转运对IBF的影响，为IBF的损伤防治提供新的研究思路及靶点。

Tight junction(TJ) plays a critical role in the maintenance of intestinal barrier function(IBF). The destruction of TJ is not only due to the altered expression of TJ proteins, but also due to the abnormally membrane trafficking of TJ proteins. So far, the regulatory mechanism of membrane trafficking have not been fully elucidated. Recently studies and our previous work have demonstrated that Par-3 may be involved in the membrane trafficking of TJ proteins in intestinal epithelial cells. Meanwhile, Par-3 can control the function of myosin II. Recent data also has revealed a requirement for myosin II in the migration of transport carriers that formed at the trans Golgi network (TGN) and were destined for the cell surface. We hypothesize that the Par-3 may disturb Golgi-membrane trafficking of TJ proteins through regulation of myosin II. Therefore, this study will investigate the role and regulatory mechanism of altered Golgi-membrane trafficking of TJ proteins in the loss of IBF both in vivo and in vitro models, utilizing RNA interference, laser confocal microscopy technique and so on. Thus, this study will inaugurate a new way for the research of IBF injury mechanism and its prevention.