抑制CD26/二肽酰肽酶Ⅳ的活性减轻移植肺缺血再灌注损伤

目的 探讨抑制CD26/二肽酰肽酶Ⅳ(DPP Ⅳ)的活性对移植肺缺血再灌注损伤的影响.方法 实验分两组进行,采用简化套管技术进行Lewis大鼠左肺原位移植,实验组的供肺以含特异性不可逆的DPP Ⅳ抑制剂AB192(终浓度为25 μmol/L)的4 ℃低钾右旋糖苷液灌洗及保存,对照组的供肺以4 ℃低钾右旋糖苷液灌洗及保存.供肺保存18 h后进行移植.分别于气管插管后、进入左胸腔、再灌注前以及再灌注后1、5、10、15 min记录受者气道的峰值压力(PawP),其后每15 min记录1次.再灌注2 h末,抽取移植肺静脉血,测定血氧分压(PO2),切取移植肺,测定移植肺组织湿重/干重比值和硫代巴比妥酸反应物(TBARS)的含量.结果 再灌注2 h后,实验组的PO2为(298.4±87.6)mm Hg,明显高于对照组的(120.9±48.0)mm Hg(P＜0.01);实验组移植肺组织湿重/干重比值为6.5±0.8,明显低于对照组的8.6±0.6(P＜0.01);实验组移植肺组织中TBARS的含量为(9.3±2.0)μmol/g,明显低于对照组的(13.8±1.8)μmol/g(P＜0.01).整个再灌注期间(2 h共14个时点),两组间PawP的差异有统计学意义(P＜0.01);再灌注2 h末,实验组的PawP为(11.8±0.9)mm Hg,显著低于对照组的(16.0±1.4)mm Hg(P＜0.01).结论 通过抑制肺组织内CD26/DPP Ⅳ的活性,可以明显减轻移植肺的缺血再灌注损伤.

Inhibiting intragraft DPP Ⅳ enzymatic activity attenuates pulmonary ischemia-reperfusion injury following transplantation

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.