异丙酚预处理对大鼠离体心脏缺血再灌注时心肌线粒体的影响

Effects of propofol preconditioning on myocardial mitochondria following ischemia-reperfusion in isolated rat hearts

目的探讨异丙酚预处理对大鼠离体心脏缺血再灌注时心肌线粒体的影响。方法成年雄性SD大鼠60只,体重250～300 g,随机分为5组（n=12）：对照组（Con组）、缺血再灌注组（I/R）和不同浓度异丙酚组（P1组、P2组、P3组）。采用Langendorpf离体心脏灌注模型,用K-H液平衡20 min后,Con组继续用K-H液灌注130 min;I/R组用K-H液灌注40 min,缺血30 min,再灌注60 min;P1组、P2组、P3组于缺血前分别用含50、100、150μmol/L异丙酚的K-H液灌注10 min,再用K-H液冲洗10 min,该过程总共进行2次为预处理,预处理后各组处理均同I/R组。记录平衡20 min（基础值）、缺血前即刻、再灌注60min的心率（HR）、左心室舒张末压（LVEDP）、左心室发展压（LVDP）、左心室压力上升及下降速率最大值（±dP/dtmax）、冠脉流量（CF）。于再灌注60 min时测定心肌梗死面积以及线粒体电子传递链Ⅰ复合体活性。结果与Con组比较,再灌注60 min时I/R组LVEDP升高,HR、LVDP、±dP/dtmax、CF均下降,P2组和P3组LVEDP升高,I/R组和P1组心肌梗死面积增大,I/R组、P1组、P2组和P3组线粒体电子传递链Ⅰ复合体活性降低（P〈0.05）;与I/R组比较,P2组及P3组再灌注60 min时LVEDP降低,HR、LVDP、±dP/dtmax、CF均升高,P2组及P3组心肌梗死面积减小,P2组和P3组线粒体电子传递链复合体Ⅰ活性升高（P〈0.05）。结论100、150μmol/L异丙酚预处理通过增加心肌线粒体电子传递链复合体Ⅰ的活性,在一定程度上减轻大鼠心肌缺血再灌注损伤。

Objective To investigate the effects of propofol preconditioning on myocardial mitochondria following ischemia-reperfusion （I/R） in isolated rat hearts .Methods Sixty adult male SD rats weighing 250-300 g were randomly divided into 5 groups （n = 12 each） ： control group （C） ; I/R group and 3 propofol preconditioning groups （P1, P2 ,P3 ）. The animals were anesthetized with intraperitoneal pentobarbital 30 mg/kg and heparinized. The hearts were excised and retrogradely perfused with K-H buffer saturated with 95% O2 and 5% CO2 at 10 kPa and 37℃ in a Langendorff apparatus. After a 20 min stabilization period the hearts were subjected to 30 min ischemia followed by 60 min reperfusion in group I/R. In the 3 propofol preconditioning groups the hearts were perfused with K-H buffer containing propofol 50, 100 and 150 μmol/L respectively for 10 min twice at 10 min intervals before I/R. Left ventricular end-diastolic pressure （LVEDP） and left ventricular developed pressure （LVDP） were measured from a fluid-filled balloon in left ventricle. LVEDP, LVDP, ＋ dp/dtmax, HR and coronary flow （CF） were measured at the end of 20 min stabilization period （baseline）, immediately before ischemia and at the end of 60 min reperfusion. The size of myocardial infarct and complex Ⅰ activity in mitochondrial electron transfer chain were measured at the end of 60 rain reperfusion. Results I/R significantly increased LVEDP and infarct size and decreased LVDP, ± dp/dt HR, CF and activity of complex Ⅰ in mitochondrial electron transfer chain as compared with control group. Preconditioning with propofol 100 or 150 μmol/L significantly attenuated the cardiac function depression, the increase in infarct size and decrease in complex Ⅰ activity induced by I/R. Conclusion Preconditioning with propofol 100 and 150 μmol/L can protect myocardium against I/R injury by increasing the activity of complex Ⅰ in mitochondrial electron transfer chain.