在糖尿病创面再上皮化障碍中Glucose/AMPK/CFTR轴对上皮间质可塑性的动态调节机制

再上皮化障碍（RED）是糖尿病皮肤创面延迟愈合（DWH）的关键事件，与DWH恶化及慢性难愈性创面发生密切相关，目前RED调控机制还未阐明，制约临床治疗发展。因此寻找RED相关的新分子靶标重要而急切。我们前期研究发现创面再上皮化（RE）角质细胞（KCs）先发生上皮间质转化（EMT），后期发生间质上皮转化（MET），具有上皮间质可塑性（EMP）特征；伴随EMP改变，腺苷酸活化蛋白激酶（AMPK）和囊性纤维化跨膜转导调节因子（CFTR）出现先下调后上调的有秩序变化；高浓度葡萄糖（glucose）诱导KCs细胞发生MET并AMPK及CFTR蛋白上调表达。本项目以Glucose/AMPK/CFTR间相互作用作为切入点，建立高糖处理KCs细胞体外培养模型及糖尿病大鼠DWH模型，模拟RED过程，应用AMPK激活剂干预，研究KCs细胞EMP相关变化规律，为糖尿病RED调控的分子机理研究提供新证据。

Re-epithelialization disorder (RED) is a key event of delayed wound healing (DWH) in diabetes mellitus. It is closely related to the deterioration of DWH and the occurrence of chronic refractory wound. At present, the regulatory mechanism of RED has not been clarified, which restricts the development of clinical treatment. Therefore, it is important and urgent to find new molecular targets related to RED. In our previous study, we found that the RE keratinocytes (KCs) first undergo epithelial-mesenchymal transformation (EMT) during wound healing, and later undergo mesenchymal-epithelial transformation (MET), which is characterized by epithelial plasticity (EMP). At the same time, AMP activated protein kinase (AMPK) and cystic fibrosis transmembrane conductance regulator(CFTR) are down regulated and up regulated in an orderly manner.High level glucose induced the EMT and upregulated the expression of AMPK and CFTR of KCs cell. In this project, the interaction between glucose / AMPK / CFTR was used as the starting point to establish KCs cell culture model in vitro and DWH model in diabetic rats, to simulate the process of RED, and to study the dynamic changes of EMP status of KCs cells by the intervention of AMPK activator, so as to provide new experimental evidence for the study of molecular regulatory mechanism of diabetic RED issues.