小肠上皮细胞（IEC）G1期阻滞在克罗恩病（CD）中具有重要意义，可致小肠上皮萎缩、更新及修复受阻等病变，但IEC G1期阻滞的调控机制未明。我们前期研究证实晚期氧化蛋白产物（AOPP）在CD患者体内蓄积，并活化ROS-JNK/ERK诱导IEC凋亡、下调其钙通道蛋白表达，而研究表明JNK/ERK是调控细胞周期的重要通路。预实验显示AOPP可诱导IEC G1期阻滞，并上调细胞周期负调控因子p27的表达。因此，我们推测AOPP通过激活ROS-JNK/ERK-p27信号诱导IEC G1期阻滞。本项目拟研究①AOPP诱导IECs G1期阻滞的分子机制，包括受体途径，ROS-JNK/ERK-p27信号及下游的周期蛋白及激酶；②阻断AOPP生物学效应对IEC G1期阻滞和CD的干预作用。从分子-细胞-组织水平阐明AOPP诱导IEC G1期阻滞的作用及机制，为揭示CD发生发展的机制并为其防治提供新思路。

G1-phase arrest of intestinal epithelial cells(IEC) plays an important role in Crohn’s disease(CD), and it causes epithelial atrophy, affects epithelial renewal and reproduction. However, the regulatory mechanism of IEC G1-phase arrest is unknown. Our previous study verified that advanced oxidation protein products (AOPP) aberrantly accumulated in diseased intestinal tissues of patients with CD, induced intestinal cell death, and decreased the expression of calcium transport channels via the ROS-JNK/ERK signaling pathway, which suggested that AOPPs may play a role in CD. And recent studies have demonstrated that JNK/ERK are important pathways in regulating cell cycle. Our preliminary experiment further showed that AOPP can induce IEC G1-phase arrest and upregulate the expression of p27--negative regulator of the cell cycle. Therefore, we speculate that AOPP can induce IEC G1-phase arrest through activating the ROS-JNK/ERK-p27 signaling pathway. Following work: (1) explore the molecular mechanism underlying AOPP induce G1-phase arrest of IEC, including receptor pathway, ROS-JNK/ERK-p27 signal and the downstream cell cycle protein and cyclin-dependent kinase; (2) investigate the effect of blocking the cell signal pathways on AOPP-induced IEC G1-phase arrest, and the intervention effect of CD. Our study will clarify the role and mechanism of AOPP-induced IEC G1-phase arrest, thus providing a new view of the pathogenic mechanism of CD and a new way to prevention and treatment of CD.