Hämoxygenase-1 führt zu endogener Bilirubinproduktion und trägt zur Manifestation des Leberschadens bei
| Autor: | S. Messner, S. Matt, Kathrin Abel, Martin K. Schilling, S. Goger, Stefan Scheingraber, Michael D. Menger |
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| Jazyk: | němčina |
| Rok vydání: | 2007 |
| Předmět: |
Liver injury
medicine.medical_specialty Chemistry Bilirubin Acute-phase protein Extrahepatic Cholestasis medicine.disease medicine.disease_cause digestive system digestive system diseases chemistry.chemical_compound Endocrinology ddc: 610 Internal medicine Immunochemistry medicine Immunohistochemistry Heme Oxidative stress |
| Zdroj: | 124. Kongress der Deutschen Gesellschaft für Chirurgie; 20070501-20070504; München; DOC07dgch7763 /20071001/ Chirurgisches Forum 2007 ISBN: 9783540711223 |
| Popis: | Background: Extrahepatic cholestasis by biliary obstruction is known to induce an acute phase reaction in the liver. The activation of acute phase proteins was related to the increase of oxidative stress. Hemeoxygenase (HO)-1 catalyses not only the degradation of endogenously produced heme, but represents also a stress protein which modulates acute inflammatory states by carbon monoxide and biliverdin formation. We have already shown that acute bile duct ligation (BDL) leads to HO-1 expression in liver tissue. In this study we focused on the contribution of HO-1 to the bilirubin production during BDL. Moreover we examined whether HO-1 has any protective role in the BDL model. Methods: Sprague Dawley rats (6 of each group) underwent BDL or Sham operation. One group with BDL or with Sham operation received additionally 10 µmol/kgKG Tin(IV)-mesoporphyrin IX (SnMP) i. v. for functional blockade of HO-1. After 3 days liver microcirculation was determined by laser Doppler flowmetry (LDF) and blood as well as liver samples were taken for further analysis (liver chemistry, histological analysis, HO-1 RT-PCR and immunohistochemistry). Results: HO-1 RNA was 2.5-fold increased after SnMP administration. Immunochemistry demonstrated 11 ± 1 % HO-1 positive hepatocytes compared to 1 ± 0.4 % in sham operated animals. Administration of SnMP further increased the percentage of HO-1 positive hepatocytes after BDL (16 ± 1 %) and even in sham operated controls (4 ± 1 %). HO-1 blockade diminished endogeneous bilirubin formation after BDL (Bilirubin BDL-group: 9.6 ± 0.4 mg/dl, BDL+SnMP-group: 6.7 ± 0.5 mg/dl). Liver injury markers such as AST and LDH were lower in the BDL+SnMP group compared to animals with BDL only. LDF showed decreased flux values in BDL compared to sham controls. Of interest, microcirculatory blood flow was even more decreased in the BDL+SnMP group. In general, liver architecture was preserved in all groups. However, there were signs of leukocyte infiltration and damage in the periportal regions in BDL and BDL+SnMP animals. Conclusions: These findings illustrate that the bilirubin increase after BDL is partially caused by increased HO-1 induction. In contrast to a large body of studies showing protective effects of HO-1 induction, our findings also suggest some detrimental effects of cholestatic HO-1 expression. |
| Databáze: | OpenAIRE |
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