异丙酚对家兔心肌缺血/再灌注损伤后心肌线粒体钙稳态的影响

Effects of propofol on calcium homeostasis of mitochondria in rabbit cardiac muscle subjected to ischemia-reperfusion injury

目的 研究异丙酚对家兔心肌在高钾停搏液保护下经历缺血再灌注后心肌线粒体钙稳态的影响。方法 采用改良Langendorff离体灌注兔心脏模型 ,用高钾停搏液使心脏停跳缺血 1h后再灌注 0 5h ,用超微电镜观察线粒体结构的变化 ,采用荧光法测量基质钙离子浓度和测量线粒体在高钙环境中的摄钙能力和加入钠离子后的释钙能力。结果 5 0 μmol L和 2 0 0 μmol L的异丙酚并不能影响再灌注对线粒体钙浓度的升高作用 ,但电镜下异丙酚组的线粒体结构损伤相对较轻。结论 临床浓度的异丙酚不是通过抑制钙内流 。

Objective To determine the effect of propofol on calcium homeostasis mitochondria in rabbit cardiac muscle subjected to ischemia reperfusion under the protection of cardioplegic solution Methods Twenty four healthy New Zealand white rabbits weighing 1 9 2 2kg were randomly divided into four equal groups of six rabbits each: control group(C);ischemia group(I); low concentration propofol +ischemia(LP) and high concentration propofol +ischemia(HP) The animals were anesthetized with intraperitoneal thiopental 25mg/kg and heparinized Chest was quickly opened and heart excised and connected to Langgendorff preparation The isolated heart was passively perfused via aorta In group LP and HP the perfusate contained propofol 50μmol/L and 200μmol/L respectively When the developed pressure of left ventricle and heat rate were stabilized (about 20 min after perfusion was stared),in group C perfusion was continued for another 90 min at normothermia (37℃±0 2℃)and 7 84kPa perfusion pressure In group I, LP and HP perfusion was stopped and cardiac arrest was induced by 20ml high potassium cardioplegic solution (4℃)and heart was immersed in 8℃ 14℃ normal saline Cardioplegic solution was perfused every 20min After 60 min cardiac arrest the heart was reperfused for another 30min The heart was then removed and immediately kept in 0℃ hemogeneous medium A slice of cardiac muscle was taken from apex of the heart Mitochondrial structure was observed using electron microscope Mitochondrial matrix calcium concentration, mitochondrial calcium uptake in high calcium enviroment (2 5 mmol/L CaCl 2 was added ) and calcium release (when sodium ion was added) were determined Results Propofol at concentration of either 50μmol/L or 200μmol/L had no effect on mitochondrial calcium homeostasis after ischemia reperfusion The damage to mitochondrial structure in propofol groups was milder than that in ischemia group Conclusions Propofol at clinical concentration can relieve the mitochondrial permeability transition pore opening at reperfusion stage The mechanism is not through inhibition of mitochondrial calcium overload, probably a result of diminished oxidative stress