Expression of BCL-2 in liver grafts after adenoviral transfer improves survival following prolonged ischemia and reperfusion in rat liver transplantation
| Autor: | A. Beham, Markus Rentsch, Thomas Müller, N. Engelhard, K. Kienle, M. Vogel, K W. Jauch |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Pathology medicine.medical_specialty medicine.medical_treatment Ischemia Liver transplantation Virus Replication medicine.disease_cause Adenoviridae Western blot medicine Animals Doxycycline Transplantation medicine.diagnostic_test business.industry Graft Survival Gene Transfer Techniques medicine.disease Genes bcl-2 Liver Transplantation Rats Gene Expression Regulation Apoptosis Reperfusion Injury Rat liver Cancer research Surgery business Reperfusion injury medicine.drug |
| Zdroj: | Transplantation Proceedings. 37:439-441 |
| ISSN: | 0041-1345 |
| DOI: | 10.1016/j.transproceed.2004.12.268 |
| Popis: | Apoptosis represents a crucial mechanism of ischemia-reperfusion injury after liver transplantation. Bcl-2 may inhibit apoptosis. This study investigates the effect on ischemia/ reperfusion injury and survival after rat liver transplantation of adenoviral bcl-2 transfer into donor livers. Methods. A nonreplicative adenovirus, expressing bcl-2 under control of a tetracyclin-inducible promoter (adv TetOn bcl-2) was used to treat male Lewis rats in combination with a second adenovirus transferring the TetOn repressor protein under control of a cytomegalovirus promoter (advCMVRep). Virus induction was achieved by addition of doxycyclin to the drinking water. Controls were pretreated with a control adenovirus (advCMV GFP) or with doxycycline. Liver transplantations were performed after 16-hour graft storage. Bcl-2 expression was evaluated by Western blot and immunohistology. Survival was monitored for 7 days, and tissue specimens were collected at 24 hours and 7 days post reperfusion. Results. After pretreatment with advTetOn bcl-2/adv CMVRep, intrahepatic bcl-2 expression was evident at 24 hours and 7 days but was absent among controls. Bcl-2 expression was detected in hepatocytes and, to a high degree, in sinusoidal lining cells. TUNEL-positive sinusoidal lining cells were strikingly reduced after bcl-2 transfer (0.1 ′ 0.3 cells/hpf, mean ′ SD) compared to control virus (4.8 ′ 2.3) or doxycyclin-treated grafts (1.3 ′ 0.2); P |
| Databáze: | OpenAIRE |
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