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二肽酰肽酶Ⅳ抑制剂灌洗、保存供肺对大鼠移植肺功能的影响

The effect of perfusion and preservation with intragraft DPP Ⅳ catalytic inhibitor on pulmonary function after lung transplantation in rats

摘要目的 探讨二肽酰肽酶Ⅳ(DPPⅣ酶)抑制剂灌洗、保存供肺对大鼠移植肺功能的影响.方法 将纯系SD大鼠随机分为6组,供、受者均为SD大鼠.对照组1和对照组2的供肺用低钾右旋糖苷液(LPD液)灌洗,并保存18 h,然后行左肺移植,于移植后1 d测定对照组1受者的气道峰压(PIP)、静脉血氧分压(POe)、移植肺湿干重比(W/D)、髓过氧化物酶(MPO)活性和丙二醛(MDA)含量,对照组2用于观察术后7 d存活率;共设4个实验组(实验组1~实验组4),供肺用含特异性不可逆DPPⅣ酶抑制剂的LPD液灌洗,并保存18 h,然后行左肺移植,分别于移植后1(实验组1)、3(实验组2)、5(实验组3)和7 d(实验组4)测定受者的各项肺功能指标.结果 对照组2大鼠至术后第7天全部死亡,实验组4的大鼠均存活至术后第7天.与对照组1比较,各实验组的PIP值降低(P<0.05),PO2值升高(P<0.05),W/D值降低(P<0.05),MPO活性及MDA含量降低(P<0.05),差异有统计学意义,并且随着时间的推移,实验组的上述指标不断改善,至术后第7天,各项检测值接近正常.结论 以特异性不可逆DPPⅣ酶活性抑制剂灌洗、保存供肺能显著减轻移植肺的缺血再灌注损伤,有利于移植肺功能的恢复.

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abstractsObjective To investigate the effect of perfusion and preservation with intragraft dipeptidyl peptidase Ⅳ (DPP Ⅳ) catalytic inhibitor on pulmonary function after lung transplantation in rats. Methods Pure SD rats were divided into six groups. Syngeneic rats (SD to SD) served as donors and recipients. Orthotopic lung transplantation model was used. Grafts of control groups (CONI and CON2) were flushed and preserved in LPD-glucoae exposed to 18 h of cold ischemia before transplantation. Peak airway pressure (PIP), blood gas (PO2), wet/dry weight ratio (W/D), the activity of myeloperoxidase (MPO) and the content of malonyldialdehyde (MDA) of CON1 group were analyzed at first day after transplantation. In CON2 group, the 7-day survival rate post-transplantation was observed. Experimental groups were divided into four sub-groups (EXP1-EXP4), and grafts were perfused and stored for 18 h with LPD-glueose plus DPPⅣ catalytic inhibitor. The pulmonary function was detected at 1st (EXP1), 3rd (EXP2), 5th (EXP3), and 7th day (EXP4) posttransplantation, respectively. Results The rats in CON2 were died at 7th day post-transplantation,and all rats in EXP4 group survived to the 7th day post-transplantation. As compared with CON1 group, PIP, W/D, MPO activity and MDA content were reduced (P<0. 01 or 0. 05), and PO2 increased (P<0. 05) in EXP4 group. The pulmonary function of DPPⅣ catalytic inhibitor-perfused grafts from 1 to 7 days was improved and all tested parameters were close to normal at 7th day.Conclusion Perfusion and preservation with an inhibitor of CD26/DPP Ⅳ enzymatic activity obviously reduced severity of ischemia-reperfusion injury and was beneficial to the rehabilitation of grafts'pulmonary function.

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