Neue Aspekte der postoperativen Darmatonie[*]

Zusammenfassung.

Darmfunktionsstörungen zählen zu den häufigsten Komplikationen nach chirurgischen Eingriffen. Verschiedene, zum Teil kontroverse Theorien über die zugrunde liegenden Pathomechanismen wurden entwickelt, ohne dass die Pathogenese bisher geklärt werden konnte. Wir konnten nachweisen, dass es nach chirurgischer Manipulation des Darmes zu einer massiven zellulären Entzündungsreaktion innerhalb der intestinalen Tunica muscularis kommt. Im Rahmen dieser Entzündung kommt es frühzeitig zur Aktivierung residenter Muscularis-Makrophagen. Diese Aktivierung wird von einer frühen, passageren Muskelfunktionshemmung begleitet. Im weiteren Entzündungsgeschehen exprimieren die Muscularis-Makrophagen proinflammatorische Zytokine (u. a. IL-1β, IL-6 und TNF-α), aktivieren Transkriptionsfaktoren (STAT, NF-κB) und führen zu einer lokalen Aufregulierung von Adhäsionsmolekülen (u. a. ICAM-1, P-Selectin, LFA-1) in der Muscularis. Die nachfolgende Rekrutierung leukozytärer Entzündungszellen geht einher mit einer längerfristigen Einschränkung der Muskelfunktion. Induzierbares Stickstoffmonoxid und Prostaglandine unterstützen die Muskelinhibition. Die selektive Blockade von induzierbarer Stickstoffmonoxid-Synthase (iNOS) oder Cyclooxygenase-2 (COX-2) führt zu einer signifikanten Reduktion der lokalen Entzündungsreaktion und einer Verbesserung der Muskelfunktion. Zusammenfassend wurden neue Mechanismen in der Entstehung postoperativer muskulärer Darmfunktionsstörungen nachgewiesen, bei welchen den residenten Makrophagen der Darmmuscularis und den induzierbaren Synthasen iNOS und COX-2 zentrale Rollen zukommen.

New aspects of postoperative ileus.

Postoperative ileus typically appears after abdominal surgery. Until now there are no conclusive theories for the pathogenesis of postoperative intestinal dysmotility. Recent investigations have studied early and late mechanisms leading to postoperative ileus by focussing on the circular muscularis externa layer of the intestinal wall. We were able to demonstrate that manipulation of the intestine caused a massive cellular inflammation within the intestinal muscle layer. This inflammatory response is preceded by the very early activation of resident macrophages within the circular intestinal muscle, which is accompanied by an early suppression of smooth muscle contractility. Muscularis macrophages express an array of various cytokines (IL-1β, IL-6 und TNF-α), transcription factors (STAT, NF-κB) and adhesion molecules (ICAM-1, P-Selectin, LFA-1). The subsequent recruitment of leukocytes is followed by a more sustained suppression of intestinal muscle contractility, which is mediated by NO and prostaglandins. The selective inhibition of iNOS and COX-2 helped to reduce the local inflammation significantly within the intestinal muscularis as well as the postoperative suppression of the muscle contractility. In summary we have shown new mechanisms responsible for postoperative ileus, in which resident muscularis macrophages as well as iNOS and COX-2 play a key role.

Schlüsselwörter:

Darmmanipulation - Makrophagen - Leukozyten - iNOS - Cyclooxygenase-2

Key words:

Postoperative ileus - Muscularis macrophages - Nitric oxide - Prostaglandins

1 Herrn Prof. H.-D. Röher zum 65. Geburtstag gewidmet.Die Arbeit wurde durch folgende Stipendien gefördert:
Schw 745/1-1 und Ka 1270/1-1 der DFG, sowie BONFOR 0-112.0006.

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1 Herrn Prof. H.-D. Röher zum 65. Geburtstag gewidmet.Die Arbeit wurde durch folgende Stipendien gefördert:
Schw 745/1-1 und Ka 1270/1-1 der DFG, sowie BONFOR 0-112.0006.