Department of Surgery, University of Alberta, 2-14A Zeidler Building, Edmonton, T6G 2X8 Alberta, Canada.
J Surg Res. 2012 Nov;178(1):147-54. doi: 10.1016/j.jss.2012.01.048. Epub 2012 Mar 31.
Crohn's disease recurrence after an ileocecal resection is common; yet, its pathophysiology is poorly understood and available treatment is suboptimal. The purpose of this study was to examine the bacterial, local, and systemic immune changes that follow ileocolonic anastomosis in a rodent model of Crohn's disease, the interleukin-10 gene-deficient (IL-10 null) mice.
We divided wild-type and IL-10 null mice into three treatment groups: ileocolonic anastomosis, sham operation (ileo-ileal anastomosis), and control group without an operation. We sacrificed mice at 6 and 15 wks after the operation. At 6 wks, we assessed bacterial changes using the denaturing gel electrophoresis and similarity coefficient calculation. At both time points, we examined the small bowel for inflammation and fibrosis with histology. We measured the interferon gamma secretion by splenocytes stimulated with gastrointestinal bacterial antigens and splenocyte composition as a marker of systemic response.
At 6 wks, ileocolonic anastomosis resulted in increased similarity in bacterial species between the ileum and colon. The ileocolonic anastomosis did not lead to significant inflammation in the small intestine, but it resulted in an increased collagen deposition in all animals undergoing surgery, the most pronounced fibrosis of which was present in IL-10 null mice 15 wks after ileocolonic anastomosis. Furthermore, this was associated with significantly increased interferon gamma secretion by bacterial antigen-stimulated splenocytes and a decreased number of CD11+ cells in the same experimental group.
Ileocolonic anastomosis leads to bacterial changes in the terminal ileum. In the genetically susceptible host, it is associated with small bowel fibrosis and systemic immune alterations. The composition of immune cells in the spleen is altered and splenocytes hypersecrete proinflammatory cytokine (interferon gamma) when challenged with gastrointestinal bacterial antigens.
回肠末端切除术后克罗恩病的复发很常见，但发病机制尚不清楚，现有的治疗方法也不尽人意。本研究的目的是在克罗恩病的一种啮齿动物模型（白细胞介素 10 基因缺陷（IL-10 缺失）小鼠）中，研究回结肠吻合术后细菌、局部和全身免疫的变化。
我们将野生型和 IL-10 缺失的小鼠分为三组：回结肠吻合组、假手术（回肠-回肠吻合术）组和无手术对照组。术后 6 周和 15 周处死小鼠。在 6 周时，我们使用变性凝胶电泳和相似系数计算来评估细菌变化。在两个时间点，我们通过组织学检查小肠的炎症和纤维化。我们测量了胃肠道细菌抗原刺激的脾细胞分泌干扰素γ和脾细胞组成，作为全身反应的标志物。
在 6 周时，回结肠吻合导致回肠和结肠之间细菌种类的相似性增加。回肠结肠吻合术在小肠中并未导致明显的炎症，但所有接受手术的动物均导致胶原沉积增加，其中 IL-10 缺失的小鼠在回肠结肠吻合术后 15 周时纤维化最为明显。此外，这与细菌抗原刺激的脾细胞分泌干扰素γ显著增加以及同一实验组 CD11+细胞数量减少有关。
回肠结肠吻合导致末端回肠的细菌变化。在遗传易感宿主中，它与小肠纤维化和全身免疫改变有关。脾细胞中免疫细胞的组成发生改变，当受到胃肠道细菌抗原的刺激时，脾细胞过度分泌促炎细胞因子（干扰素γ）。
