Publikationsserver der Universitätsbibliothek Marburg

Titel:Untersuchungen zur Prostaglandinabhängigen Pathogenese des antenatalen Bartter-Syndroms am Zellmodell primär kultivierter Nierenepithelzellen
Autor:Simon, Friederike
Weitere Beteiligte: Nüsing, Rolf (Prof. Dr.)
Veröffentlicht:2013
URI:https://archiv.ub.uni-marburg.de/diss/z2013/0455
URN: urn:nbn:de:hebis:04-z2013-04551
DOI: https://doi.org/10.17192/z2013.0455
DDC: Medizin
Titel (trans.):Analysis of the prostaglandine dependent pathogenesis of the antenatal Bartter Syndrome on a cell modell of primary cultivated renal epithelial cells
Publikationsdatum:2013-08-13
Lizenz:https://rightsstatements.org/vocab/InC-NC/1.0/

Dokument

Schlagwörter:
hyperprostaglandine E syndrome, Hypoosmolarität, antenatales Bartter Syndrom, Prostaglandines, Zellmodell primär kultivierter Nierenepithelzellen, Hyperprostaglandin-E-Syndrom, Prostaglandine, Hypoosmolarity

Zusammenfassung:
Leitsymptome des Hyperprostaglandinsyndroms sind neben einer erhöhten renalen Salz- und Wasserausscheidung eine verstärkte Reninproduktion, eine Hyperkalzurie und eine Hypertrophie des juxtaglomerulären Apparates. Bereits pränatal kommt es zur Ausbildung einer fetalen Polyurie, welche zur Ausbildung eines Polyhydramnions führen kann. Hierin ist die extrem gesteigerte Frühgeburtlichkeitsrate zwischen der 28. und 34. SSW begründet. Für die klinischen Symptome Durst, Fieber und Wachstumsbeeinträchtigungen wird v. a. eine massiv erhöhte renale Ausscheidung von PGE2 verantwortlich gemacht. In der vorliegenden Arbeit wurde anhand von primär kultivierten Schweinenierenzellen des dicken aufsteigenden Teils der Henle-Schleife, die Regulation der Prostaglandinsynthese näher untersucht und der Einfluss von Elektrolyten überprüft. Nach Stimulation mit hypotoner Lösung wurde eine Zunahme der PGE2-Synthese, der Expression der mPGES-1 mRNA und der COX-1 und COX-2 mRNA sowie eine Zunahme des Proteins der COX-2 beobachtet. Welche Art der Elektrolytveränderung hierfür ausschlaggebend ist, v. a. ob der Chloridentzug der maßgebliche Faktor ist, muss in Experimenten weiter geklärt werden. Unter isoosmolaren Bedingungen zeigte sich ebenfalls eine Expression der PGES-1, allerdings weniger deutlich als nach Stimulation mit hypoosmolarem Medium. Somit lässt sich durchaus eine Beteiligung der PGES-1 an der PGE2-Bildung bei Veränderung des zellulären Salzhaushaltes vermuten. Meine Ergebnisse geben darüber hinaus Anlass anzunehmen, dass die gesteigerte Prostaglandinsynthese MAP Kinase-gesteuert ist. Zur genaueren Aufklärung der beteiligten Faktoren und Wirkmechanismen müssen weitere Experimente erfolgen. Die klinische Relevanz weiterer Untersuchungen wird deutlich, wenn man bedenkt, dass der einzige therapeutische Ansatz der Salzverlusttubulopathien momentan die Hemmung der Prostaglandinsynthese darstellt. Es fehlen auch grundlegende Erkenntnisse über das COX-1/COX-2 Gleichgewicht im menschlichen Körper, welche für die Entwicklung weiterer Therapien notwendig sind. Mit dem Zellmodell konnten erste Regulationsmechanismen aufgedeckt werden, es eignet sich aber sicherlich auch dazu weitere Abläufe dieses Zellsystems näher zu untersuchen.

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