Türler Andreas, Schnurr Christoph, Nakao Atsunori, Tögel Sandra, Moore Beverley A, Murase Noriko, Kalff Jörg C, Bauer Anthony J
Department of Medicine, Division of Gastroenterology, University of Pittsburgh Medical Center, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
Ann Surg. 2007 May;245(5):734-44. doi: 10.1097/01.sla.0000255595.98041.6b.
To investigate muscularis inflammation and endogenous endotoxin as causes of postoperative ileus.
Postoperative inflammatory ileus of the colon is associated with a significant delay in gastrointestinal transit. We investigated whether these changes are caused by the downstream obstructive barrier of the surgically altered colon or by small intestinal muscularis inflammation itself. Furthermore, we evaluated the mechanistic role of gut derived endotoxin in the development of postoperative intestinal dysfunction.
Rats underwent surgical manipulation of the colon. Isolated gastrointestinal transit was analyzed in animals with ileostomy. The perioperative emigration of intracolonic particles was investigated by colonic luminal injection of fluorescently labeled LPS and microspheres. Mediator mRNA induction was quantified by real-time RT-PCR. Muscularis leukocytic infiltrates were characterized. In vitro circular muscle contractility was assessed in a standard organ bath.
Ileostomy rats presented with a significant delay in small intestinal transit after colonic manipulation. This was associated with leukocyte recruitment and inflammatory mediator mRNA induction within the small intestinal muscularis. Colonic manipulation caused the transference of intracolonic LPS and microspheres into the intestinal muscularis. Postoperative in vitro small intestinal circular muscle contractility was impaired by 42% compared with controls. Gut decontamination and TLR-4 deletion significantly alleviated the small intestinal muscularis inflammation and prevented intestinal muscle dysfunction.
Selective colonic manipulation initiates a distant inflammatory response in the small intestinal muscularis that contributes to postoperative ileus. The data provide evidence that gut-derived bacterial products are mechanistically involved in the initiation of this remote inflammatory cascade.
研究肌层炎症和内源性内毒素作为术后肠梗阻病因的情况。
结肠术后炎症性肠梗阻与胃肠运输的显著延迟相关。我们研究了这些变化是由手术改变的结肠的下游阻塞性屏障引起，还是由小肠肌层炎症本身引起。此外，我们评估了肠道源性内毒素在术后肠道功能障碍发生中的机制作用。
对大鼠进行结肠手术操作。对回肠造口术动物的孤立胃肠运输进行分析。通过向结肠腔内注射荧光标记的脂多糖（LPS）和微球来研究围手术期结肠内颗粒的迁移。通过实时逆转录聚合酶链反应（RT-PCR）对介质mRNA诱导进行定量。对肌层白细胞浸润进行特征描述。在标准器官浴中评估体外环形肌收缩力。
结肠操作后，回肠造口术大鼠的小肠运输出现显著延迟。这与小肠肌层内的白细胞募集和炎症介质mRNA诱导有关。结肠操作导致结肠内LPS和微球转移到肠肌层。与对照组相比，术后体外小肠环形肌收缩力受损42%。肠道去污和Toll样受体4（TLR-4）缺失显著减轻了小肠肌层炎症并预防了肠肌功能障碍。
选择性结肠操作引发小肠肌层的远处炎症反应，这导致了术后肠梗阻。数据提供了证据表明肠道源性细菌产物在这一远程炎症级联反应的启动中具有机制性作用。
