Kalff J C, Carlos T M, Schraut W H, Billiar T R, Simmons R L, Bauer A J
Departments of Surgery and Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Gastroenterology. 1999 Aug;117(2):378-87. doi: 10.1053/gast.1999.0029900378.
BACKGROUND & AIMS: Postoperative ileus is a poorly understood and common problem. We previously demonstrated an association between a suppression in jejunal circular muscle activity and a massive extravasation of leukocytes into the muscularis after surgical manipulation of the small bowel. This study was pursued to establish a direct causal link between these events.
Reverse-transcription polymerase chain reaction and immunohistochemistry were used to detect and localize expression of adhesion molecules: P-selectin, intercellular adhesion molecule 1 (ICAM-1), and lymphocyte function-associated antigen 1 (LFA-1). Leukocyte infiltration and in vitro jejunal circular muscle function were quantified in controls and manipulated animals with and without antibody treatment (1A29, WT.1, and WT.3).
Surgical manipulation caused a significant up-regulation within the muscularis of ICAM-1 and P-selectin messenger RNA. ICAM-1 and P-selectin protein expression was increased within the muscularis microvasculature, and ICAM-1 and LFA-1 were expressed on infiltrating cells. Administration of adhesion molecule antibodies prevented the recruitment of monocytes and neutrophils into the muscularis and also averted jejunal circular muscle dysfunction.
The data demonstrate that adhesion molecule antibodies prevent surgically induced suppression of intestinal muscle contractions and therefore suggests that late postoperative ileus is mediated through a leukocytic inflammatory response within the intestinal muscularis externa.
术后肠梗阻是一个尚未被充分理解的常见问题。我们之前证明了空肠环行肌活动受抑制与小肠手术操作后白细胞大量外渗至肌层之间存在关联。本研究旨在确立这些事件之间的直接因果关系。
采用逆转录聚合酶链反应和免疫组织化学方法检测并定位黏附分子的表达：P-选择素、细胞间黏附分子1（ICAM-1）和淋巴细胞功能相关抗原1（LFA-1）。对对照组以及接受手术操作且接受或未接受抗体治疗（1A29、WT.1和WT.3）的动物，定量白细胞浸润和体外空肠环行肌功能。
手术操作导致肌层内ICAM-1和P-选择素信使核糖核酸显著上调。ICAM-1和P-选择素蛋白表达在肌层微脉管系统内增加，且ICAM-1和LFA-1在浸润细胞上表达。给予黏附分子抗体可阻止单核细胞和中性粒细胞募集至肌层，还可避免空肠环行肌功能障碍。
数据表明黏附分子抗体可防止手术诱导的肠道肌肉收缩抑制，因此提示术后晚期肠梗阻是通过肠外肌层内的白细胞炎症反应介导的。
