Department of Medicine/Gastroenterology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Cytokine. 2012 Jul;59(1):49-58. doi: 10.1016/j.cyto.2012.03.012. Epub 2012 Apr 12.
Ileus is caused by the initiation of a complex cascade of molecular and cellular inflammatory responses within the intestinal muscularis, which might be species specific. Our objective was to investigate a possible immunological divergence in the mechanisms of postoperative- and endotoxin-induced ileus in C57BL/6 mice and Sprague-Dawley rats. Gastrointestinal transit (GIT) was measured at 24 h after the injurious stimulus. MPO-staining and F4/80 immunohistochemistry were used to quantify polymorphonuclear and monocyte infiltration of jejunal muscularis whole-mounts, and intestinal muscularis MCP-1, ICAM-1 and iNOS gene expression was assessed by RT-PCR. Intestinal muscularis subjected to in vivo surgical manipulation (SM) or LPS treatment was cultured for 24 h, and the liberation of nitric oxide and chemokines/cytokines into the culture medium was analyzed by Griess reaction and Luminex multiplex assay. Intestinal SM and lipopolysaccharide (LPS) (15 mg/kg) caused a significant delay in gastrointestinal transit, which was more severe in mice compared to rats in both injury models. Both SM- and LPS-triggered neutrophil and monocytic extravasation into the rat jejunal muscularis exceeded the cellular infiltration seen in mice. These results correlated with significantly greater increases in rat muscularis MCP-1 (syn. CCL2), ICAM-1 and iNOS message with more subsequent NO production after SM or LPS compared to mouse. The cultured muscularis obtained from SM mice released significantly more inflammatory proteins such as TNF-α, IL-1-α, IL-4 and GM-CSF compared to the manipulated rat muscularis. In contrast, LPS initiated the secretion of significantly more IL-1β by the inflamed rat muscularis compared to the mouse, but GM-CSF (syn. CSF2) liberation from mouse muscularis was markedly higher compared to LPS-treated rat muscularis. The data indicate that mechanistically the development of ileus in rat is mediated predominately through a leukocytic pathway consisting of chemotaxis, cellular extravasation and NO liberation. Whereas, the more intense mouse ileus evolves via a potent but injury-specific local cytokine response.
肠麻痹是由肠道肌层内复杂的分子和细胞炎症反应级联反应引起的，这种反应可能具有种属特异性。我们的目的是研究术后和内毒素诱导的 C57BL/6 小鼠和 Sprague-Dawley 大鼠肠麻痹的机制是否存在免疫差异。在损伤刺激后 24 小时测量胃肠道转运（GIT）。使用髓过氧化物酶（MPO）染色和 F4/80 免疫组化来定量 jejunal 肌层全层的多形核白细胞和单核细胞浸润，通过 RT-PCR 评估肠道肌层 MCP-1、ICAM-1 和 iNOS 基因表达。对体内手术操作（SM）或 LPS 处理后的肠道肌层进行 24 小时培养，通过 Griess 反应和 Luminex 多重分析测定培养物中一氧化氮和趋化因子/细胞因子的释放。肠 SM 和脂多糖（LPS）（15mg/kg）导致胃肠道转运明显延迟，在两种损伤模型中，与大鼠相比，小鼠的延迟更为严重。SM 和 LPS 触发的中性粒细胞和单核细胞渗出到大鼠空肠肌层的程度超过了小鼠的细胞浸润程度。这些结果与大鼠肌层 MCP-1（syn. CCL2）、ICAM-1 和 iNOS 基因表达的显著增加相关，与小鼠相比，SM 或 LPS 后产生更多的一氧化氮。与操纵后的大鼠肌层相比，来自 SM 小鼠的培养肌层释放的 TNF-α、IL-1-α、IL-4 和 GM-CSF 等炎症蛋白明显更多。相反，与 LPS 处理的大鼠肌层相比，LPS 启动了炎症大鼠肌层中更多的 IL-1β 的分泌，但 GM-CSF（syn. CSF2）从鼠肌层的释放明显高于 LPS 处理的大鼠肌层。数据表明，在机制上，大鼠肠麻痹的发展主要通过由趋化、细胞渗出和一氧化氮释放组成的白细胞途径介导。相比之下，更严重的小鼠肠麻痹通过一种强烈但具有损伤特异性的局部细胞因子反应发展。
