七氟烷预处理对糖尿病大鼠离体心肌缺血-再灌注损伤的影响

摘要

Objective To investigate the effect of sevoflurane preconditioning on myocardial ischemia-reperfusion(I-R) injury in isolated rats with diabetes mellitus (DM ) .Methods Sixty-four male SD rats were randomly divided into four groups of D(DM rats with I-R injury) ,DS(DM rats with sevoflurane preconditioning and I-R injury) ,N(nonDM rats with I-R injury) and NS(nonDM rats with preconditioning and I-R injury) .The hearts isolated from all rats were experienced ischemia for 30 minutes and followed by reperfusion .The hearts in groups of NS and DS were perfused with K-H solution saturated with 2.4% sevoflurane for 10 minutes before ischemia ,which was followed by 5 minutes washout .The cardiac function variables were measured at 20 minutes of equilibrium ,15 ,60 minutes of reperfusion .Cardiocyte apoptotic index (CAI) and expressions of phosphorylated Akt (p-Akt) and total Akt were measured with TUNEL staining and Western blot analysis at 15 minutes of reperfusion .The infarcted size of the myocardium (ISM ) was measured with TTC staining at the end of reperfusion . Results Compared with group N ,group NS showed significant decreases in CAI and ISM companied by an increase of expression of p-Akt at 15 minutes of reperfusion and an improved hemodynamic function(P<0 .05) .There were no significant differences in the parameters mentioned above between groups of D and DS(P>0 .05) .Compared with group N ,group D showed significant decreases in CAI and ISM companied by increased expression of p-Akt at 15 minutes of reperfusion and improved hemodynamic function(P<0 .05) .Conclusion Sevoflurane preconditioning can effectively protect the hearts from I-R injury in isolated hearts from normal rats .Sevoflurane preconditioning can not protect the hearts of DM rats ,for which lossing increase of Akt activation may be one of the mechanisms .%目的 观察七氟烷预处理对糖尿病(DM )模型大鼠离体心肌缺血-再灌注(I-R)损伤的影响.方法 雄性SD大鼠64只 ,随机均分为四组 :N组 ,非DM ,I-R;NS组 ,非DM ,I-R前七氟烷预处理 ;D组 ,DM ,I-R;DS组 ,DM ,I-R前七氟烷预处理.采用大鼠离体心脏Langendorff灌注模型 ,行全心缺血30 min ,再灌注60 min.NS组和DS组于缺血前用2. 4% 七氟烷预充饱和的K-H液灌注10 min ,洗脱5 min.记录各组平衡末及再灌注15、60 min的心功能指标 ,TUNEL法检测再灌注15 min心肌细胞凋亡 ,Western blot法半定量检测磷酸化和总丝氨酸/苏氨酸激酶(Akt) ,再灌注末采用氯化三苯基四氮唑染色分析心肌梗死面积百分比.结果 与N组相比 ,NS组再灌注15 min心肌细胞凋亡减少 ,伴随磷酸化Akt表达增强(P<0 .05) ,再灌注末心功能指标改善(P<0 .05) ,心肌梗死面积减小(P<0 .05).D组与DS组间上述指标未见统计学差异(P>0 .05).与N组比较 ,D组基础心功能指标降低(P<0 .05) ,而再灌注15 min心肌细胞凋亡减少伴随磷酸化Akt表达增强 ,再灌注末心功能恢复增强(P<0 .05) ,心肌梗死面积下降(P<0 .05).结论 七氟烷预处理可以减轻非DM 大鼠心肌I-R损伤;其在DM大鼠没有显示心肌保护作用 ,心肌Akt活化水平不能有效提高可能是其机制之一.