特异性磷酸二酯酶抑制剂对老年供体肺保存的干预

Effect of phosphodiesterase inhibitor on senile lung function during preservation period

目的:利用大鼠离体肺再灌注模型,应用特异性磷酸二酯酶抑制剂米力农在器官摘取及保存期处理老年大鼠供体肺,观察其对老年供体肺保存效果的影响。方法:实验于2006-10/12在阜外心血管病研究所实验外科完成。①实验分组及方法:选用20周龄SD大鼠24只及SD老年大鼠12只,将大鼠按随机数字表法分为3组:对照组(6只年轻大鼠→6只年轻大鼠),建立大鼠离体肺再灌注模型,低钾右旋糖酐液灌洗后摘取心肺器官,4℃恒温冰箱中保存12h后取出,以5mL/min流量再灌注60min。老年大鼠供体常规保存组(6只老年大鼠→6只年轻大鼠),按其体质量配相应灌洗液量,余同对照组。米力农处理老年大鼠供体组(6只老年大鼠→6只年轻大鼠),供体肺灌洗液及保存液中含有666μg/L米力农,余同老年大鼠供体常规保存组。②实验评估:观察各组大鼠供体肺流出血氧分压、平均肺动脉压、肺气道压力动态变化及再灌注后供体肺湿干比、肺组织丙二醛含量及髓过氧化物酶活性。结果:36只大鼠全部进入结果分析。①随着灌注时间的延长,老年大鼠供体常规保存组大鼠各时间段供体肺的流出血氧分压均低于对照组(P<0.05),平均肺动脉压均高于对照组(P<0.05),再灌注40min和60min时的肺气道压力高于对照组(P<0.05)。而米力农处理老年大鼠供体组与对照组差异均无显著性意义(P>0.05)。②老年大鼠供体常规保存组再灌注后供体肺湿干比、肺组织丙二醛含量及髓过氧化物酶活性均显著高于对照组(P<0.05),米力农处理老年大鼠供体组与对照组差异无显著性意义(P>0.05)。结论:特异性磷酸二酯酶抑制剂米力农药物处理老年供体肺能够减轻缺血再灌注损伤,明显改善移植后早期老年供体肺功能。

AIM： To study the protective effect of agent mildnone, a kind of specific phosphodiesterase inhibitor, on senile grafts during graft procurement and cold preservation period. METHODS： The experiment was conducted in the Department of Surgery, Fuwai Cardiovascular Institute from October to December 2006. ①Twenty-four 20-week-old SD rats and 12 one-year-old SD rats were randomly divided into 3 groups. In control group （6 young rats as donors, and another 6 as recipients）, the rungs were tfushed with low potassium dextran （LPD） solution and preserved in refrigerator at 4℃ for 12 hours, followed by 60 minutes reperfusion at 5 mL/min. Preservation group （6 senile rats as donors and 6 young rats as recipients） was washed with corresponding solution according to their body mass, and then treated with the same method as control group. In milr（none group （6 senile rats as donors and 6 young rats as recipients）, there was 666 μg/L milrinone in LPD solution and the rest was the same as group preservation group. ②The oxygen partial pressure, mean pulmonary arterial pressure （MPAP）, lung airway pressure changes, ratio of lung wet weight and dry weight after reperfusion, malondialdehyde （MDA） content in lung tissue and myeloperoxidase （MPO） of donor lung in each group were observed. RESULTS： All 36 rats were involved in the result analysis. （~With the reperfusion, the oxygen partial pressure of preservation group at each stage was lower than that in control group （P 〈 0.05）, MPAP was higher than that in control group （P 〈 0.05）, airway pressure was higher than control group after 40 and 60 minutes reperfusion （P 〈 0.05）. However, there was no significant difference between milrinone group and control group （P 〉 0.05）. ~）The wet/dry ratio, MDA content and MPO activity in preservation group after reperfusion were significantly higher than those in control group （P 〈 0.05）, but no difference was found between mildnone group and control group （P 〉 0.05）, CONCLUSION= Phosphodiesterase inhibitor milrinone protects senile grafts from ischemia/reperfusion injury and remarkably improve early lung function after pulmonary transplantation during cold storage period.