Dokument: Beeinflussung der Immunantwort in der moderaten Sepsis durch die moderate Hyperkapnie und die Modulation des K+-ATP-Kanals

Titel:	Beeinflussung der Immunantwort in der moderaten Sepsis durch die moderate Hyperkapnie und die Modulation des K+-ATP-Kanals
URL für Lesezeichen:	https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=56975
URN (NBN):	urn:nbn:de:hbz:061-20210728-104312-6
Kollektion:	Dissertationen
Sprache:	Deutsch
Dokumententyp:	Wissenschaftliche Abschlussarbeiten » Dissertation
Medientyp:	Text
Autor:	Weiss, Sabrina [Autor]
Dateien:	[Dateien anzeigen] Adobe PDF [Details] 776,4 KB in einer Datei [ZIP-Datei erzeugen] Dateien vom 23.07.2021 / geändert 23.07.2021
Beitragende:	Prof. Dr. Picker, Olaf [Gutachter] PD Dr. Niegisch, Günter [Gutachter]
Dewey Dezimal-Klassifikation:	600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit
Beschreibungen:	Einleitung: Eine moderate Hyperkapnie scheint neben vasoaktiven Effekten auch die Immunantwort möglicherweise über die Inhibition des ATP sensitiven Kaliumkanals (K+ATP-Kanal) zu beeinflussen. Dies könnte ein weiterer Erklärungsansatz für den protektiven Effekt der Hyperkapnie in der Sepsis sein. Ziel dieser Doktorarbeit war es daher zu untersuchen, welchen Einfluss eine moderate Hyperkapnie auf die systemische wie lokale Immunantwort in der Sepsis hat und ob diese durch die Inhibition des K+ATP-Kanals verändert werden. Methoden: Dafür wurden 40 männliche Wistar-Ratten in 4 Gruppen randomisiert (n=10). Die Sepsis-Induktion erfolgte durch eine CASP Operation. Nach 24 Stunden wurden die septischen Tiere nach vorheriger Applikation von Glibenclamid (1mg/kg/KG in 1ml NaCl i.v.) bzw. Vehikel (1ml NaCl 0,9% i.v.) für 120 Minuten entweder normokapnisch (paCO¬2 35 - 45 mmHg) oder hyperkapnisch (paCO2 65 - 75 mmHg) ventiliert. Am Ende des Experimentes erfolgte die Blutentnahme zur Messung der Zytokinplasmaspiegel (TNF-α, IL-6, IL-10) mittels ELISA. Des Weiteren wurde aus dem entnommenen Colon- und Lungengewebe eine Western Blot Analyse der Adhäsionsmoleküle ICAM-1 und E-Selectin durchgeführt und die MPO-Aktivität bestimmt. Ergebnisse: Weder die moderate Hyperkapnie noch die Gabe von Glibenclamid sowie auch deren Kombination führten zu einer signifikanten Veränderung der Zytokinplasmaspiegel. Zudem konnte kein signifikanter Unterschied zwischen den Behandlungsgruppen in der Expression der Adhäsionsmoleküle ICAM-1 und E Selectin sowie der MPO Aktivität im Colon und in der Lunge festgestellt werden. Schlussfolgerung: Die protektiven Effekte der Hyperkapnie in der Sepsis werden unabhängig von der Immunantwort und des K+ATP-Kanals vermittelt. Introduction: In addition to vasoactive effects, moderate hypercapnia might influence the immune response due to the inhibition of ATP sensitive potassium channels (K+ATP channels). This could explain the protective effect of hypercapnia in sepsis. Thus this doctoral thesis aimed to investigate the influence of moderate hypercapnia on the systemic and local immune response in sepsis and how this is affected by the inhibition of K+ATP channels. Methods: 40 male Wistar rats were randomized into 4 groups (n=10). Sepsis was induced by CASP surgery. After 24 hours septic animals were treated with glibenclamide (1mg/kg/KG) in 1ml NaCl i. v. or a vehicle (1ml NaCl 0.9% i.v.) and received either normocapnic (paCO2 35-45 mmHg) or hypercapnic (paCO2 65 75 mmHg) ventilation for 120 minutes. At the end of the intervention the cytokine plasma levels (TNF-α, IL-6, IL-10) were determined by ELISA. In addition, the adhesion molecules ICAM-1 and E-selectin in colon and lung tissue were determined by western blot analysis and MPO activity was determined by MPO Assay. Results: Neither moderate hypercapnia, nor glibenclamide, nor the combination of both significantly altered cytokine plasma levels. In addition, there was no significant difference in ICAM-1 and E-Selectin expression and intestinal or pulmonary MPO activity within the treatment groups. Conclusion: The protective effects of hypercapnia in sepsis are mediated independently of the immune response and K+ATP channels.
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Lizenz:	Urheberrechtsschutz
Fachbereich / Einrichtung:	Medizinische Fakultät
Dokument erstellt am:	28.07.2021
Dateien geändert am:	28.07.2021
Promotionsantrag am:	25.01.2021
Datum der Promotion:	08.06.2021