deguelin attenuates reperfusion injury and improves outcome after orthotopic lung transplantation in the ratdeguelin变弱后再灌注损伤,改善结果原位大鼠肺移植.pdfVIP

Deguelin Attenuates Reperfusion Injury and Improves Outcome after Orthotopic Lung Transplantation in the Rat 1 1 2 3 3 1 Patrick Paulus *, Pia Ockelmann , Sabine Tacke , Nora Karnowski , Peter Ellinghaus , Bertram Scheller , 4 5 1 Johannes Holfeld , Anja Urbschat , Kai Zacharowski 1 Clinic of Anesthesiology, Intensive Care Medicine and Pain Therapy, Goethe-University Hospital Frankfurt, Frankfurt am Main, Germany, 2 Department of Veterinary Clinical Sciences, Clinic for Small Animals Surgery, Justus-Liebig University, Giessen, Germany, 3 Clinical Pharmacology, Global Biomarker, Bayer Pharma AG, Wuppertal, Germany, 4 Clinic of Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria, 5 Clinic of Urology, Goethe-University Hospital Frankfurt am Main, Germany Abstract The main goal of adequate organ preservation is to avoid further cellular metabolism during the phase of ischemia. However, modern preservation solutions do rarely achieve this target. In donor organs hypoxia and ischemia induce a broad spectrum of pathologic molecular mechanisms favoring primary graft dysfunction (PGD) after transplantation. Increased hypoxia-induced transcriptional activity leads to increased vascular permeability which in turn is the soil of a reperfusion edema and the enhancement of a pro-inflammatory response in the graft after reperfusion. We hypothesize that inhibition of the respiration chain in mitochondria and thus inhibition of the hypoxia induced mechanisms might reduce reperfusion edema and consecutively improve survival in vivo. In this study we demonstrate that the rotenoid Deguelin reduces the expression of hypoxia induced target g