Dokument: Einfluss einer sterilen Laparotomie und einer moderaten abdominellen Sepsis auf die Mitochondrienfunktion im Darm im zeitlichen Verlauf bis 96h
| Titel: | Einfluss einer sterilen Laparotomie und einer moderaten abdominellen Sepsis auf die Mitochondrienfunktion im Darm im zeitlichen Verlauf bis 96h | |||||||
| Weiterer Titel: | Influence of a sterile laparotomy and a moderate abdominal sepsis on mitochondrial function in the gut over a time course up to 96h | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=51599 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20200110-092341-0 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Deutsch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Itta, Rebecca [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Picker, Olaf [Gutachter] Prof. Dr. med. Akhyari, Payam [Gutachter] | |||||||
| Stichwörter: | Mitchochondrien, Sepsis, CASP | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibungen: | Auch heutzutage stellt eine Sepsis mit den Folgen eines möglichen Multiorganversagens eine große Herausforderung in der Intensivmedizin dar. Sowohl eine Störung der Mikrozirkulation als auch eine mitochondriale Dysfunktion, insbesondere des Gastrointestinaltraktes, werden als ein wesentlicher pathophysiologischer Mechanismus der Sepsis angesehen. Allerdings ist bislang nicht untersucht, ob und in welchem Ausmaß Mitochondrien aus Zellen des Gastrointestinaltraktes ihre Funktion während der Sepsis verändern und welchen Einfluss bereits eine isolierte Laparotomie hat. Ziel dieser Studie war es, im Zeitverlauf über 96 h zu untersuchen, inwieweit eine Sepsis mit abdominellem Fokus zu einer mitochondrialen Dysfunktion des Darmes führt und welcher Bedeutung dabei der reinen Laparotomie (Sham OP) zukommt.
Nach Genehmigung der Tierschutzbehörde wurden 95 männliche Wistar-Ratten in 8 Gruppen (n=11-12) randomisiert: Gruppen 1-4 Sham, Gruppen 5-8 CASP. Nicht behandelte Tiere dienten als Kontrolle (n=9). Zu den Zeitpunkten 24, 48, 72 und 96 Stunden wurde die mitochondriale Funktion in Gewebehomogenaten des Colons mittels Respirometrie gemessen. Dabei wurde der mitochondriale Sauerstoffverbrauch gemessen und zwar für State 2 nach Stimulation mit den Substraten für Komplex I Glutamat/ Malat und Komplex II Succinat und für State 3 nach Stimulation mit ADP. Der „respiratory control ratio“ (RCR= State 3/ State 2) wurde als Maß der Kopplung zwischen Atmungskettenaktivität und oxidativer Phosphorylierung berechnet. Die Effizienz der oxydativen Phosphorylierung wurde durch die ADP/O-Ratio (zugegebene Menge ADP/ Verbrauchter O2) dargestellt. Zur statistischen Analyse wurde das Computerprogramm GraphPad Prism v6.01 verwendet. Dabei wurde eine two-way ANOVA mit Signifikanzniveau p<0,05 und eine Tukey post-hoc Analyse durchgeführt. Sowohl der RCR als auch die ADP/O-Ratio für beide Komplexe blieben im zeitlichen Verlauf in allen Gruppen unverändert. Die mitochondriale Funktion im Colon blieb bis zu 96h nach einer sterilen Laparotomie und bei einer moderaten abdominellen Sepsis im CASP-Modell unverändert.Even today sepsis and its most severe complication multi-organ failure are a major challenge in intensive care. Microcirculation and mitochondrial dysfunction are both considered as major pathophysiological mechanisms of sepsis. However, it has not yet been investigated whether and to which extent mitochondria from cells of the gastrointestinal tract change their function during sepsis and what influence a sterile laparotomy already has on them. The aim of this study was to investigate the effect of a sterile laparotomy and of a moderate abdominal sepsis on the mitochondrial function in colon in a time course over 96 hours. According to the animal welfare authority, 95 male Wistar rats were randomized into 8 groups (n= 11-12): 1-4 sham, 5-8 CASP. Untreated animals served as control (n= 9). The mitochondrial respiration in colon homogenates was assessed 24, 48, 72, and 96 hours after surgery. Mitochondrial oxygen consumption was determined using a Clark-type electrode. State 2 (oxygen consumption in the presence of the substrates for complexes I and II) and state 3 respiration (ADP dependent) were assessed. The respiratory control ratio (RCR= state 3/ state 2) and ADP/O ratio (ADP added/ oxygen consumed) were calculated for both complexes. Data are presented as means ± SD, two-way ANOVA followed by Tukey’s post hoc test. Both the RCR and the ADP/O-ratio for both complexes remained unchanged over the time course of 96 hours. The mitochondrial function in the colon remains unchanged up to 96 hours after a sterile laparotomy and by moderate abdominal sepsis. | |||||||
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| Lizenz: |  Urheberrechtsschutz | |||||||
| Bezug: | 2015-2019 | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 10.01.2020 | |||||||
| Dateien geändert am: | 10.01.2020 | |||||||
| Promotionsantrag am: | 29.04.2019 | |||||||
| Datum der Promotion: | 06.11.2019 |
