To Protect Fatty Livers from Ischemia Reperfusion Injury: Role of Ischemic Postconditioning.

Autor: Schewe J; Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Berlin, Germany., Makeschin MC; Department of Pathology, University Hospital, LMU Munich, Munich, Germany., Khandoga A; Department of Surgery, University Hospital, LMU Munich, Munich, Germany., Zhang J; Department of Medicine II, University Hospital, Liver Centre Munich, LMU Munich, Campus Grosshadern, Marchioninistrasse 15, 81377, Munich, Germany., Mayr D; Department of Pathology, University Hospital, LMU Munich, Munich, Germany., Rothenfußer S; Division of Clinical Pharmacology, University Hospital, LMU Munich, Munich, Germany., Schnurr M; Division of Clinical Pharmacology, University Hospital, LMU Munich, Munich, Germany., Gerbes AL; Department of Medicine II, University Hospital, Liver Centre Munich, LMU Munich, Campus Grosshadern, Marchioninistrasse 15, 81377, Munich, Germany., Steib CJ; Department of Medicine II, University Hospital, Liver Centre Munich, LMU Munich, Campus Grosshadern, Marchioninistrasse 15, 81377, Munich, Germany. christian.steib@med.uni-muenchen.de.
Jazyk: angličtina
Zdroj: Digestive diseases and sciences [Dig Dis Sci] 2021 Apr; Vol. 66 (4), pp. 1349-1359. Date of Electronic Publication: 2020 May 25.
DOI: 10.1007/s10620-020-06328-w
Abstrakt: Background: The benefit of ischemic postconditioning (IPostC) might be the throttled inflow following cold ischemia. The current study investigated advantage and mechanisms of IPostC in healthy and fatty rat livers.
Methods: Male SD rats received a high-fat diet to induce fatty livers. Isolated liver perfusion was performed after 24 h ischemia at 4 °C as well as in vivo experiments after 90 min warm ischemia. The so-called follow-up perfusions served to investigate the hypothesis that medium from IPostC experiments is less harmful. Lactate dehydrogenase (LDH), transaminases, different cytokines, and gene expressions, respectively, were measured.
Results: Fatty livers showed histologically mild inflammation and moderate to severe fat storage. IPostC reduced LDH and TXB 2 in healthy and fatty livers and increased bile flow. LDH, TNF-α, and IL-6 levels in serum decreased after warm ischemia + IPostC. The gene expressions of Tnf, IL-6, Ccl2, and Ripk3 were downregulated in vivo after IPostC.
Conclusions: IPostC showed protective effects after ischemia in situ and in vivo in healthy and fatty livers. Restricted cyclic inflow was an important mechanism and further suggested involvement of necroptosis. IPostC represents a promising and easy intervention to improve outcomes after transplantation.
Databáze: MEDLINE
Externí odkaz: