基于Notch-1信号通路研究肠系膜侧的微环境影响克罗恩病术后吻合口复发的机制

Crohn’s disease (CD) is a kind of chronic intestinal inflammatory disease and characterized with prominent postoperative anastomotic recurrence, which persists in annoying patients received surgery. The differences of vessels supplied within mesenteric side walls result in embolism and the clinic evidences implied that anastomasis involved the mesenteric side prompting the recurrence. Early-stage experiments discovered that such signaling as Notch-1 possess disparities between different walls of intestine. In addition, inhibiting Notch-1 signaling brings benefits to the expression of inflammatory factors and VEGF, which are co-cultured by intestine epithelial cells and lamina propria lymphocytes from intestinal walls. This project aims at detecting the expression of Notch-1 signal existing in mesenteric sides and anti-mesenteric sides, during and after surgery. Then try to figure out the rough role played by mesenteric microenvironment in recurrence of CD and evaluate the feasibility of Notch-1 signaling as prognostic factor for recurrence. By culturing immune cells separated from mesenteric sides and anti-mesenteric sides with epithelial cells, we could then get a concept on molecular mechanism of mesenteric microenvironment influenced by Notch-1 signaling in vitro. Finally, conducting anastomasis on CD rat model with mesenteric side involved or not and impacting Notch-1 signaling to further study the influence on recurrence from mesenteric microenvironment. It is expected to guide the methods of anastomasis in surgery of CD and shed a new light on the theoretical basis for postoperative treatment.

克罗恩病（CD）是一慢性肠道炎症疾病，其术后吻合口高复发率是外科治疗亟待解决的问题。系膜侧壁的血供差异导致其易发生栓塞，且临床研究提示涉及肠系膜侧壁的吻合方式更易复发。前期实验发现Notch-1等分子在系膜侧和对系膜侧表现出明显差异，且抑制Notch-1信号可改善肠上皮细胞与肠壁分离免疫细胞共培养中的炎症因子和VEGF等的表达。本项目拟在术中及术后复发标本中检测系膜侧和对系膜侧Notch-1信号等因子的表达，初步探讨系膜侧微环境在复发中的地位并评估系膜侧Notch-1信号通路作为术后复发检测指标的价值。随后通过体外分离系膜侧和对系膜侧的免疫细胞，与肠上皮细胞共培养，研究Notch-1信号参与系膜侧微环境建立的分子机制。最后在大鼠模型中通过涉及/不涉及系膜侧两种吻合方式并尝试干预吻合口Notch-1信号，研究系膜侧微环境对复发影响，为CD手术吻合方式选择和术后干预提供理论依据和新的思路。

克罗恩病（CD）是一慢性肠道炎症疾病，其术后吻合口高复发率是外科治疗亟待解决的问题。我们通过对术中的标本进行检测证明Notch-1等分子在手术切缘区的系膜侧和对系膜侧表现出明显差异，病灶区差异不明显。对术后活检标本的检测和随访，我们发现侧侧吻合口的Notch-1等分子的表达会随时间显著少于端侧吻合口的相应分子的表达，而且侧侧吻合方式的预后效果要好于端侧吻合。我们初步探讨系膜侧微环境在复发中的地位并评估系膜侧Notch-1信号通路作为术后复发检测指标的价值，通过体外分离系膜侧和对系膜侧的免疫细胞，与肠上皮细胞共培养，研究Notch-1信号参与系膜侧血管生成微环境建立的分子机制，我们证明了抑制Notch-1信号可改善肠上皮细胞与肠壁分离免疫细胞共培养中的炎症因子和VEGF等的表达。最后在大鼠模型中通过涉及/不涉及系膜侧两种损伤方式并尝试干预损伤处的Notch-1信号，研究证明了系膜侧微环境对复发有影响，为CD手术吻合方式选择和术后干预提供理论依据和新的思路。

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