Grotz M, Regel G, Schratt H E, Seekamp A, Pape H C, Tscherne H
Unfallchirurgische Klinik, Medizinische Hochschule Hannover.
Z Gastroenterol. 1996 Dec;34(12):783-90.
Intestinal ischemia, frequently found in clinical states such as aortic bypass operations or hemorrhagic shock, is associated with loss of gut barrier function. Subsequent translocation of indigenous bacteria and endotoxin have been implicated as a major contributor to a systemic immuno-inflammatory response, which finally leads to multiple organ failure. There is increasing evidence that intestinal injury can result in the gut becoming a cytokine generating organ. This study was designed to show direct evidence of the gut as a major source of proinflammatory cytokines after intestinal ischemia and to further relate this cytokine response to the extent of intestinal ischemia/reperfusion. Additionally the potential role of the altered intestinal barrier function after intestinal ischemia for this cytokine response was investigated.
Rats were subjected to occlusion of the superior mesenteric artery for 45 min. (SMAO45), 75 min. (SMAO75), SMAO for 45 min. and 30 min. reperfusion (SMAO45/30), or sham SMAO, and then killed. Mucosal membranes from the terminal ileum were mounted in a Ussing chamber. E. coli C25 was added to the mucosal side of the stripped gut epithelium in half of the chambers. TNF and IL-6 levels on mucosal and serosal side of the stripped gut epithelium were assessed serially over 3 hrs. Gut barrier function was assessed by in vitro bacterial translocation (BT) and the transepithelial resistance (TER) of the mucosal membrane.
The TNF response was greatest in the SMAO75 group, the IL-6 response in the SMAO75 and SMAO45/30 groups. In the absence of E. coli C25. IL-6 was produced to a greater extent on the serosal side, while addition of bacteria led to a significantly increased TNF/IL-6 response at the mucosal side of the stripped gut epithelium. BT was increased in SMAO75 and SMAO45/30 rats. Baseline TER was decreased in all experimental compared to sham SMAO groups. Although gut barrier function was impaired after intestinal ischemia/reperfusion there was no correlation between intestinal cytokine response and gut permeability.
The gut becomes a cytokine liberating organ alter intestinal ischemia/reperfusion. This cytokine response is affected by certain conditions, but is not directly related to an impaired intestinal barrier function.
肠道缺血常见于主动脉搭桥手术或失血性休克等临床状态，与肠道屏障功能丧失有关。随后，肠道内细菌和内毒素的易位被认为是导致全身免疫炎症反应的主要因素，最终可导致多器官功能衰竭。越来越多的证据表明，肠道损伤可使肠道成为细胞因子产生器官。本研究旨在直接证明肠道是肠道缺血后促炎细胞因子的主要来源，并进一步将这种细胞因子反应与肠道缺血/再灌注的程度联系起来。此外，还研究了肠道缺血后肠道屏障功能改变对这种细胞因子反应的潜在作用。
将大鼠肠系膜上动脉阻断45分钟（SMAO45）、75分钟（SMAO75）、阻断45分钟后再灌注30分钟（SMAO45/30），或进行假手术，然后处死。将回肠末端的黏膜置于尤斯灌流小室中。在一半的小室中，将大肠杆菌C25添加到剥离的肠上皮黏膜侧。在3小时内连续评估剥离的肠上皮黏膜侧和浆膜侧的TNF和IL-6水平。通过体外细菌易位（BT）和黏膜膜的跨上皮电阻（TER）评估肠道屏障功能。
TNF反应在SMAO75组中最大，IL-6反应在SMAO75和SMAO45/30组中最大。在没有大肠杆菌C25的情况下，IL-6在浆膜侧产生的程度更大，而添加细菌导致剥离的肠上皮黏膜侧的TNF/IL-6反应显著增加。SMAO75和SMAO45/30大鼠的BT增加。与假手术组相比，所有实验组的基线TER均降低。尽管肠道缺血/再灌注后肠道屏障功能受损，但肠道细胞因子反应与肠道通透性之间没有相关性。
肠道缺血/再灌注后，肠道成为释放细胞因子的器官。这种细胞因子反应受某些条件影响，但与肠道屏障功能受损无直接关系。
