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Heme oxygenase-1 overexpression increases liver injury after bile duct ligation in rats

World Journal of Gastroenterology 2007年第25期13卷 3478-3486页

作者： Matthias Froh Lars Conzelmann Peter Walbrun Susanne Netter Reiner Wiest Michael D Wheeler Mark Lehnert takehiko uesugi Jurgen Scholmerich Ronald G Thurman Department of Internal Medicine University of Regensburg Germany Department of Urology University of Mainz Germany Department of Pharmacology University of North Carolina United States

AIM： To investigate the effects of heme oxygenase-1 （HO-1） against oxidant-induced injury caused by bile duct ligation （BDL）.METHODS： Either cobalt protoporphyrin （CoPP）, a HO-1 inducer, or saline were injected intraperitoneally in male SD-rats. Three days later, BDL or sham-operations were performed. Rats were sacrificed 3 wk after BDL and livers were harvested for histology. Fibrosis was evaluated by sirius red staining and image analysis. Alpha-smooth muscular actin, which indicates activation of stellate cells, was detected by immunohistochemical staining, and q/tokine and collagen- Iα （Col- I α） mRNA expression was detected using RNase protection assays.RESULTS： Serum alanine transaminase increased 8-fold above normal levels one day after BDL. Surprisingly, enzyme release was not reduced in rats receiving CoPP. Liver fibrosis was evaluated 3 wk after BDL and the sirius red-positive area was found to be increased to about 7.8%. However, in CoPP pretreated rats sirius redpositive areas were increased to about 11.7% after BDL. Collagen-1 α and TGF-β mRNA increased significantly by BDL. Again, this effect was increased by HO-1 overexpression.CONCLUSION： Hepatic fibrosis due to BDL is not reduced by the HO-1 inducer CoPP. In contrast, HO-1 overexpression increases liver injury in rats under conditions of experimental chronic cholestasis.

关键词： Heme oxygenase-1 Bile duct ligation Chronic cholestasis Liver fibrosis Serum alaninetransaminase Transforming growth factor-13 Tumornecrosis factor- I ~ Type I collagen

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