Department of Pathophysiology, Institute of Digestive Disease, Tongji University School of Medicine, Shanghai, China.
PLoS One. 2013 Jul 3;8(7):e67427. doi: 10.1371/journal.pone.0067427. Print 2013.
Intestinal inflammatory responses play a critical role in the pathogenesis of postoperative ileus (POI). As cannabinoid receptor-1 (CB1) is involved in inhibiting gastrointestinal (GI) motility and anti-inflammation, we aimed to explore its contribution to POI.
Experimental POI was induced in adult female CB1-deficient (CB1-/-) mice and wild-type littermates (C57BL/6N) by standardized small bowel manipulation. Twenty-four hours after surgery, GI transit was assessed by charcoal transport. FITC avidin, F4/80, and myeloperoxidase immunohistochemistry techniques were used to evaluate the inflammatory response in the muscularis of ileum and colon. Expressions of p38MAPK and its phosphorylated form (pp38) in the intestine were determined. Plasma levels of proinflammatory cytokines and chemokines were measured by ELISA as well.
POI was characterized by decreased GI transit (p<0.01) and accompanied by a marked intestinal and systematic inflammatory response in wild-type and CB1-/- mice. Increased numbers of inflammatory cells, including macrophages, neutrophils, and mast cells were observed in the muscularis of ileum and colon (p<0.01, or p<0.05). Plasma levels of interleukin-6 (IL-6), cytokine-induced neutrophil chemoattractant-1 (CINC-1/KC), and monocyte chemoattractant protein-1 (MCP-1) were elevated (p<0.01, or p<0.05). Expression of p38 and pp38 increased in the intestine (p<0.01, or p<0.05). CB1-/- mice showed an increased inflammatory response during POI, especially the systemic inflammatory markers, such as IL-6, KC, CINC1, and pp38 expression were increased as compared to those in WT mice (p<0.05).
Intestinal motility was inhibited during POI. In this condition, inhibition of motility did not seem to be altered by the absence of CB1 receptors, however, an increased inflammatory response was observed in CB1-/- mice. Hence, CB1 receptor activation rather than inhibition may reduce the inflammatory response in POI, which has a remote potential to relate into reduced inhibition of intestinal motility during POI.
肠道炎症反应在术后肠梗阻（POI）的发病机制中起着关键作用。由于大麻素受体 1（CB1）参与抑制胃肠道（GI）蠕动和抗炎作用，我们旨在探索其对 POI 的贡献。
通过标准化的小肠操作，在成年雌性 CB1 缺陷（CB1-/-）小鼠和野生型同窝仔（C57BL/6N）中诱导实验性 POI。手术 24 小时后，通过炭素转运评估 GI 转运。FITC 亲和素、F4/80 和髓过氧化物酶免疫组织化学技术用于评估回肠和结肠肌层的炎症反应。通过免疫印迹法测定肠道中 p38MAPK 及其磷酸化形式（pp38）的表达。通过 ELISA 测量血浆中促炎细胞因子和趋化因子的水平。
POI 的特征是 GI 转运减少（p<0.01），并且在野生型和 CB1-/- 小鼠中伴有明显的肠道和系统性炎症反应。在回肠和结肠肌层中观察到炎症细胞数量增加，包括巨噬细胞、中性粒细胞和肥大细胞（p<0.01 或 p<0.05）。白细胞介素-6（IL-6）、细胞因子诱导的中性粒细胞趋化因子-1（CINC-1/KC）和单核细胞趋化蛋白-1（MCP-1）的血浆水平升高（p<0.01 或 p<0.05）。肠道中 p38 和 pp38 的表达增加（p<0.01 或 p<0.05）。在 POI 期间，CB1-/- 小鼠表现出增强的炎症反应，特别是系统炎症标志物，如 IL-6、KC、CINC1 和 pp38 的表达增加，与 WT 小鼠相比（p<0.05）。
POI 期间肠道蠕动受到抑制。在这种情况下，缺乏 CB1 受体似乎不会改变运动的抑制，但在 CB1-/- 小鼠中观察到炎症反应增强。因此，CB1 受体的激活而不是抑制可能会减少 POI 中的炎症反应，这可能与 POI 期间肠道蠕动抑制的减少有关。
