肠道淋巴管功能障碍会引起脂质外漏、脂质沉积。脂肪组织通过释放脂肪因子及细胞因子参与克罗恩病(CD)的病理生理。肠淋巴管结构及功能异常是CD的重要病理特征，但其中的机制尚不明确。Prospero同源蛋白1(Prox1)具有促进淋巴管增生及维持淋巴管结构及功能的作用。我们前期研究发现肠淋巴系统的病理性改变与CD的疾病进程显著相关、CD肠道组织Prox1的表达显著异常、上调Prox1的表达能够显著减轻CD模型小鼠的结肠炎症。本课题在前期工作基础上，以CD患者组织标本及CD模型小鼠为研究对象，通过分子生物学及分子免疫学等技术，研究肠淋巴系统结构异常及功能障碍在CD病理生理中的作用及其机制，探讨Prox1对CD动物模型的作用、对肠淋巴系统结构及功能的调节作用，并以淋巴内皮细胞为切入点，探索Prox1对CD肠淋巴系统的作用机制，为揭示CD 病理生理、为CD防治提供依据及新的靶点。

Lymph flow is a critical player of intestinal lipids proteins, and other particles transport. Lymphatic obstruction, and remodeled and impaired contraction may lead to lipids leakage and fat deposition. Through release of the adipokines and cytokines, accumulated fat mass exerts its effects in the initiation or aggravation of intestinal inflammation in Crohn's disease (CD). Enlarged or obstructed-lymphatic vessels are important pathological features in patients with CD, supporting the notion that intestinal lymphatics are important player in the pathogenesis of CD although the exact mechanism remains unknown. Prox1 (prospero homeobox protein 1), a homeobox transcription factor, is a critical regulator of lymphatic system development and is critical for lymphatic endothelial cells differentiation. In our recent work, changes of mesenteric lymphatic system were demonstrated to be correlated with recurrence of CD, and Prox1 was found to be expressed in the intestine for patients with CD. In mice with colitis, Prox1 knock out was associated with acceleration of colonic inflammation, implying the participation of Prox1 in the pathogenesis of CD. To further explore the role of intestinal lymphatics in the pathogenesis of CD, the therapeutic effects and the underlying mechanisms of Prox1 pathway in this process, we propose the current project based on a combination of in vivo and in vitro studies. In this propose study, molecular biology, histology, and electrophysiology will be applied for carrying out this experiment evaluate the morphological and functional changes of intestinal lymphatic system in CD, the therapeutic effects and the potential mechanisms of Prox1. Results from our study may provide evidence for the pathogenesis of CD and for the clinical utility in the management of CD.