肠粘膜屏障是放射线肠道毒性作用的主要靶标，肠屏障损伤诱发放射线肠炎（RE），是影响放疗进程的重要因素，但目前对RE缺乏有效的治疗和预防手段。我们前期研究表明肠上皮分子Syndecan-1（Sdc1）能明显减轻肠道炎症反应，阻止多种致病因素作用于肠道，维护肠屏障功能，但其在RE中的作用并不明确。进一步生物信息学分析提示Sdc1是miR-221/222的潜在靶基因，而miR-221/222的表达会受到被放射线激活的P65因子的直接调控。因此我们提出一个RE肠粘膜屏障损伤的新机制：放疗中NF-kB通路被激活，通过启动miR-221/222转录、靶向抑制Sdc1，破坏肠粘膜屏障功能，引起RE；补充Sdc1可能发挥防治RE的保护作用。我们将采用X线刺激、过表达、RNA干扰等方法，以及ChIP和双荧光素酶报告基因实验等分子生物学手段，从体内、外对这一假设进行探讨，将为临床RE的防治提供新思路和新靶点。

Intestinal barrier is the primary enterotoxigenic target of radiation. Barrier impairment initiates radiation enteritis (RE), and postpones the process of radiation therapy. However, the efficient methods of prevention and treatment are greatly deficient. Our previous study demonstrated that cell surface Syndecan-1 (Sdc1) significantly alleviates intestinal inflammation, prevents pathogenic factors attach to intestine and maintains integrated intestinal barrier function. But whether this mechanism functions during RE remains unclear. Further bioinformatics analysis suggests that Sdc1 is a potential target of miR-221/222 cluster, and miR-221/222 is transcriptionally regulated by radiation-activated P65. Thus the hypothesis driving this proposal is that the miR-221/222 regulated Sdc1 maintains intestinal barrier during RE upon radiation activated NF-κB pathway. Multiple ways including radiation stimulation, overexpression, and RNA interference, as well as chromatin immunoprecipitation and dual-luciferase reporter system will be applied to demonstrate the proposal. Cell line, mouse model, and patients with RE will be introduced. This study will enrich our knowledge of the radiobiology of organs at risk and provide new therapeutic strategy for improving the radiotherapy outcome of patients with abdominal or pelvic cancer.