外源性阿片肽预处理对体外循环后猪肺缺血再灌注损伤的保护作用  

Exogenous opioid peptide preconditioning in prevention of pulmonary ischemia-reperfusion injury in pigs after cardiopulmonary bypass

作　　者：王亚华[1] 石学银[1] 孙继雄[2] 朱秋峰[1] 徐海涛[1] 吉玉龙[1] 袁红斌[1] 何星颖[1] 

机构地区：[1]第二军医大学长征医院麻醉科,上海200003 [2]同济大学东方医院麻醉科,上海200120

出　　处：《第二军医大学学报》2006年第11期1196-1199,共4页Academic Journal of Second Military Medical University

摘　　要：目的:观察外源性阿片肽(DADLE)对体外循环(CPB,cardiopulmonary bypass)后猪肺缺血再灌注损伤的保护作用,探讨其可能的保护机制。方法:选取28只雄性幼猪,随机分为4组(n=7),分别为假手术组(Sham组)、体外循环模型组(CPB模型组)、DADLE预处理组(DADLE组)和ATP敏感钾离子通道阻断剂(Glibenclamide)阻断组(KATP阻断组)。Sham组仅予以开胸和主动脉及上下腔静脉插管操作,其余3组均建立CPB模型,并给予各自不同的预处理。CPB术前及再灌注不同时间点(10、30、60 min)比较各组动物气道峰压(peak inspiratory pressure,PIP)、动脉血氧分压(PaO2)、血清中丙二醛(maloudialde-hyde,MDA)含量。CPB术前及再灌注60 min各组取相同部位肺组织测定肺湿干重比(wet/dry weight ratio,W/D);再灌注60min时处死动物,计算肺损伤程度(lung tissue damage,LTD)并观察肺泡上皮超微结构的改变。结果:CPB术前各组间PaO2、PIP、MDA和W/D无显著差异;Sham组各时间点上述指标无明显变化。再灌注60 min,CPB模型组和KATP阻断组PaO2明显低于Sham组和DADLE组,而PIP、MDA、W/D和LTD显著高于Sham组和DADLE组(P<0.05或0.01);DADLE组LTD高于Sham组(P<0.05),其余指标无明显差异;CPB模型组和KATP阻断组间上述指标无显著差异。肺泡上皮超微结构观察发现CPB模型组和KATP阻断组肺泡上皮细胞损伤重于Sham组和DADLE组。结论:外源性阿片肽预处理可能通过促进ATP敏感钾通道的开放保护肺功能,从而减轻CPB术后的肺缺血再灌注损伤。Objective：To evaluate the protective effect of 8-opioid peptide, [D-Ala2-D-LeuS]-enkephaline （DADLE）, on pulmonary ischemia-reperfusion （I-R） injury after cardiopulmonary bypass （CPB）, and to discuss the possible mechanism. Methods： Twenty-eight male pigs were evenly randomized divided into 4 groups, namely, the sham-operation group, the CPB group （only subjected to CPB）, the DADLE pretreatment group （received DADLE 1 mg . kg^-1 before CPB）, and the Glibenclamide group （received DADLE 1 mg . kg^-1 and glibenclamide 1 mg.kg^-1 before CPB）. Peak inspiratory pressure （PIP）, PaO2, and the plasma malondialdehyde （MDA） concentration were measured in each group before CPB and 10 min, 30 min, and 60 rain after reperfusion. The changes of lung tissue wet weight/dry weight ratio （W/D） were calculated before CPB and 60 min after reperfusion. The animals were sacrificed 60 rain after reperfusion to observe the ultrastructural changes of the lungs and to quantitatively assess lung tissue damage （LTD）. Results： There were no significant differences among the 4 groups before CPB and the parameters in sham-operation group had no changes at all specified time points. One hour after reperfusion, the PIP, MDA, W/D, and LTD values in Glibenclamide and CPB groups were significantly higher than those in sham-operation and DADLE groups while the PaO2 was significantly lower（P〈0.05 or 0.01）. There were no significant differences between parameters of sham-operation and DADLE groups except for LTD（P〈0.05）. There were no significant differences between parameters of Glibenclamide and CPB groups. Histological examination demonstrated that the degree of lung injuries in sham-operation and DADLE groups were slighter than those in Glibenclamide and CPB groups. Conclusion： It suggests that DADLE may exert its protective effect on the lung through opening ATP-sensitive K＋ channels, so as to alleviate the lung I-R injury after CPB.

关 键 词：体外循环 再灌注损伤 肺 阿片肽 

分 类 号：R619[医药卫生—外科学]