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Organ-spezifisches Expressions-muster eines Kohlenmonoxid-generierenden Streßproteins (Hämoxygenase-1/Hitzeschock-protein 32) nach hämorrhagischem Schock

Organ-specific expression pattern of a carbon monoxide-generating stress protein (haeme oxygenase-1) after haemorrhagic shock and resuscitation

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Zusammenfassung

Kohlenmonoxid (CO) entsteht als Intermediärstoffwechselprodukt im Hämabbau und kann nach neuesten Erkenntnissen ähnlich wie Stickstoffmonoxid über Aktivierung der Guanylatzyklase vasodilatorische Wirkungen entfalten. Für die endogene Bildung von CO ist ausschließlich die mikrosomale Hämoxygenase (HO) verantwortlich, die als konstitutives Enzym (HO-2) sowie in einer streßinduzierbaren Isoform (HO-1 oder Hitzeschockprotein 32) vorliegt. Hemmung des Hämstoffwechsels nach Schock und Volumentherapie führt nach eigenen Untersuchungen zu einer spezifischen Zunahme des Pfortaderwiderstands, ohne vasokonstriktorische Wirkungen in der systemischen Zirkulation hervorzurufen. In der vorliegenden Arbeit wurde daher das organspezifische Expressionsmuster der streßinduzierbaren Isoform des Enzyms nach hämorrhagischem Schock und Volumentherapie untersucht.

Methoden und Ergebnisse

In einem kliniknah therapierten Schockmodell an der Ratte führte das Schockereignis zu einer geringfügigen Expression von HO-1 in Aortengewebe sowie zu einer ausgeprägten Expression in der Leber, während eine Induktion in anderen Organen wie Lunge, Darm oder Niere nach Hämorrhagie nicht nachweisbar war.

Schlußfolgerung

Diese Ergebnisse legen nahe, daß HO-1/Hitzeschockprotein 32 in der Leber ein streßinduzierbares Vasodilatatorsystem, das zur Aufrechterhaltung der Leberperfusion nach hämorrhagischem Schock beiträgt, darstellt.

Abstract

Objective

Recent evidence suggests a possible role for Haeme oxygenase (HO)-derived carbon monoxide (CO) in the regulation of vascular tone through elevation of cyclic 3′–5′ guanosine monophosphate (cGMP). Previous work from our laboratory has shown that blockade of the HO pathway by tin-protoporphyrin-IX (SnPP) after resuscitation from haemorrhage leads to a specific and profound increase in portal resistance while neither systemic nor hepatic arterial resistance are affected. We therefore investigated the organ-specific expression pattern of the stress-inducible protein haeme oxygenase-1/heat shock protein 32 after haemorrhage and resuscitation.

Materials and methods

After approval of the protocol by the local review board, male Sprague-Dawley rats (n=6/group) were anaesthetised with pentobarbitone, instrumented for assessment of central haemodynamics, and subjected to haemorrhagic hypotension (40 mm Hg for 1 h) followed by resuscitation with 60% shed blood and Ringer’s solution or a time-matched sham protocol. Samples of liver, spleen, kidney, intestine, aorta, and lungs were harvested 5 h after the onset of resuscitation and subjected to Western-blot analysis using a specific antirat HO-1/hsp 32 antibody (StressGen, Sidney, Canada).

Results

Resuscitation with shed blood/Ringer’s solution restored central haemodynamics and acid-base status while significant haemodilution was observed. Haemorrhage and resuscitation led to strong induction of HO-1 in the liver and slight induction in aortic tissue, while no increase in steady-state protein levels was observed in the other organs studied.

Conclusion

These results suggest a specific contribution of the HO/CO pathway to maintenance of low hepatic portal resistance in vivo in a clinically relevant model of haemorrhagic shock and adequate resuscitation.

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Bauer, M., Rensing, H., Bauer, C. et al. Organ-spezifisches Expressions-muster eines Kohlenmonoxid-generierenden Streßproteins (Hämoxygenase-1/Hitzeschock-protein 32) nach hämorrhagischem Schock. Anaesthesist 46, 339–342 (1997). https://doi.org/10.1007/s001010050409

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  • DOI: https://doi.org/10.1007/s001010050409

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