Inhibiting intragraft DPP Ⅳ enzymatic activity attenuates pulmonary ischemia-reperfusion injury following transplantation
- VernacularTitle:抑制CD26/二肽酰肽酶Ⅳ的活性减轻移植肺缺血再灌注损伤
- Publication Type:Journal Article
- Keywords: Lung transplantation; Dipeptidyl peptidase; Transplants; Reperfusion injury
- From: Chinese Journal of Organ Transplantation 2008;29(5):283-285
- CountryChina
- Language:Chinese
- Abstract: Objective To investigate the effect of enzymatic DPP Ⅳ inhibition on ischemiareperfnsion (I/R) injury after extended ischemia prior to transplantation. Methods A simplified syngeneic rat (Lewis) orthotopic left lung transplantation model was used in two groups. In the control group (group Ⅰ) ,donor lungs were flushed and preserved in Perfadex (R) for 18 h at 4 ℃ ,then transplanted and reperfused for 2 h. In the treated group (group Ⅱ ) donor lungs were perfused with and stored in Perfadex (R) + 25 mol/L AB192 [bis(4-acetamidophenyi) 1-(S)-prolylpyrrolidine-2(R,S)-phosphonate],a small molecular weight DPP Ⅳ inhibitor. Peak airway pressure (PawP) was recorded after intubation, upon entering the chest, before reperfusion, at 1,5,10 and 15 min after reperfusion,and then every 15 min thereafter. At the end of a 2 h-reperfusion, blood gas analysis,PawP,wet to dry weight ratio (W/D) and thiobarbiturie acid reactive substances (TBARS) were measured. Results In grafts of group Ⅱ as compared with group Ⅰ ,oxygenation capacity was significantly greater (298.4 ±87. 6 mm Hg vs. 120. 9 ± 48.0 mm Hg, P＜0.01), PawP lower (11.8 ± 0. 9 mm Hg vs. 16.0 ±1.4 mm Hg,P＜0. 01 ) ,W/D ratio lower (6. 5 ± 0. 8 vs. 8. 6 ± 0. 6,P＜0. 01 ) and TBARS less (9. 3 ±2. 0 μmol/g vs. 13. 8 ± 1.8 μmol/g, P＜0. 01 ). Conclusion Inhibiting intragraft DPP Ⅳ enzymatic activity significantly reduces I/R-associated pulmonary injury, allowing for successful transplantation after 18 h of ischemia.