七氟醚后处理对大鼠心肌缺血再灌注时视神经萎缩症蛋白1表达的影响

Effect of sevoflurane postconditioning on expression of optic atrophy-1 during myocardial ischemia-reperfusion in rats

目的 评价七氟醚后处理对大鼠心肌缺血再灌注时视神经萎缩症蛋白1（OPA1）表达的影响.方法 健康成年雄性SD大鼠45只,3月龄,体重220 ～ 280 g,采用随机数字表法分为3组（n=15）：假手术组（S组）、缺血再灌注组（I/R组）和七氟醚后处理组（SP组）.采用结扎左冠状动脉前降支30 min再灌注120 min的方法制备心肌缺血再灌注损伤模型.S组仅穿线,不结扎左冠状动脉前降支;I/R组结扎左冠状动脉前降支后缺血30 min,再灌注120 min;SP组于再灌注前1 min吸入2.5％七氟醚,持续5 min,其余组吸入氧浓度33％的空气.分别于缺血前15 min（T0）、缺血15 min（T1）、再灌注60和120 min（T2.3）时记录HR、SP和MAP,计算RPP（HR和SP的乘积）.于再灌注120 min时取心肌组织,测定心肌梗死体积,计算心肌梗死体积百分比,分别采用免疫组化法和RT-PCR法测定OPA1蛋白及其mRNA的表达,心肌HE染色,光镜下观察病理学结果,电镜下观察心肌细胞线粒体超微结构.结果 与S组比较,I/R组和SP组T1-3时MAP和RPP降低,心肌OPA1蛋白和mRNA的表达下调,心肌梗死体积百分比升高（P＜0.05）;与I/R组比较,SP组T2,3时MAP和RPP降低,心肌OPA1 mRNA和蛋白的表达上调,心肌梗死体积百分比降低（P＜0.05）.SP组大鼠心肌病理学损伤较I/R组减轻.结论 七氟醚后处理可通过上调心肌OPA1表达,保护线粒体形态完整,进而抑制心肌细胞凋亡,减轻大鼠心肌缺血再灌注损伤.

Objective To evaluate the effect of sevoflurane postconditioning on expression of optic atrophy-1 （OPAl） during myocardial ischemia-reperfusion （I/R） in rats.Methods Forty-five healthy adult male Sprague-Dawley rats,aged 3 months,weighing 220-280 g,were randomly divided into 3 groups （n =15 each） using a random number table：sham operation group （group S）,ischemia-reperfusion group （group I/R）,and sevoflurane postconditioning group （group SP）.Myocardial ischemia was induced by 30 min occlusion of left anterior descending branch of coronary artery followed by 120 min reperfusion.2.5 % sevoflurane was inhaled for 5 min starting from 29 min of ischemia until 4 min after beginning of reperfusion in SP group,while 33 % oxygen was inhaled in the other groups.Heart rate,systolic pressure and mean arterial pressure （MAP） were monitored and recorded and rate-pressure product （RPP） was calculated at 15 min before ischemia （T0）,15 min of ischemia （T1）,and 60 and 120 min of reperfusion （T2,3）.At the end of reperfusion,the rats were sacrificed and the hearts were removed for determination of myocardial infarct size.The expression of OPAl mRNA and protein was measured by RT-PCR and immunohistochemistry,respectively.Their hearts were cut into sections which were stained with H.E.and examined under light microscope.Morphological changes of mitochondria were examined by electron microscopy.Results Compared with group S,MAP and RPP were significantly decreased at T1-3,the expression of OPA1 mRNA and protein was down-regulated,and the myocardial infarct size was increased in I/R and SP groups.Compared with group I/R,MAP and RPP were significantly decreased at T2,3,the expression of OPA1 mRNA and protein was up-regulated,and the myocardial infarct size was decreased in group SP.Conclusion Sevoflurane postconditioning can reduce myocardial I/R injury through up-regulating myocardial OPA1 expression,protecting mitochondrial morphology and inhibiting apoptosis in cardiomyocytes of rats.