- 作者：Wei Zhai ; Markus Cardell ; Ingrid De Meester ; Koen Augustyns ; Sven Hillinger ; Ilhan Inci ; Stephan Arni ; Wolfgang Jungraithmayr ; Simon Scharpé ; Walter Weder ; et al.
- 刊名：The Journal of Heart and Lung Transplantation
- 出版年：2007
- 期刊代码：161_10532498
- 类别：med
- 出版时间：February 2007
- 卷：26
- 期：2
- 页码：174-180
- 文件大小：608 K
Background
CD26/DPP IV is a T-cell-membrane protein that cleaves dipeptides from extracellular peptides. Inhibition of its enzymatic activity using Pro-Pro-diphenylphosphonate derivatives has been shown to abrogate acute and accelerated rejection in models of cardiac and pulmonary allotransplantation. Here we investigated the effects of enzymatic DPP IV inhibition on ischemia/reperfusion (I/R) injury after extended ischemia before pulmonary transplantation.Methods
A syngeneic rat orthotopic left-lung transplantation model was used. Group I donor lungs (controls) were flushed and preserved in Perfadex for 18 hours at 4°C and then transplanted and reperfused for 2 hours. Group II grafts were perfused with and stored in Perfadex + 25 μmol/liter AB192 [bis(4-acetamidophenyl) 1-(S)-prolylpyrrolidine-2(R,S)-phosphonate]. Group III lungs were perfused with Perfadex + AB192, and stored in Perfadex. After 2-hour reperfusion, oxygenation, peak airway pressure (PawP), graft wet/dry (W/D) weight ratio, myeloperoxidase activity, thiobarbituric acid–reactive substances, graft specific DPP IV enzymatic activities and histomorphology were analyzed.
Results
AB192 perfusion significantly reduced DPP IV intragraft enzymatic activity in Groups II and III. Compared with controls, transplants from Groups II and III showed significantly improved oxygenation capacity, PawP and W/D weight ratio, with lower intragraft lipid peroxidation; and preserved histologic structure.
Conclusions
Targeting intragraft DPP IV enzymatic activity attenuated post-transplantation I/R injury and preserved early graft function after extended ischemia.