异丙酚对大鼠心肌缺血再灌注时心肌细胞膜Na~+-K~+-ATP酶活性和线粒体钙含量的影响

目的 探讨异丙酚对大鼠心肌缺血再灌注时心肌细胞膜Na~+-K~+-ATP酶活性和线粒体钙含量的影响.方法 雄性SD大鼠加只,体重300～350 g,随机分为5组(n=8):假手术组(S组)、缺血再灌注组(IR组)和不同剂量异丙酚组(P1组～P3组).IR组和P1组～P3组采用结扎左冠状动脉前降支30 min,再灌注60 min的方法制备大鼠心肌缺血再灌注模型;C组仅穿线,不结扎左冠状动脉前降支.P_1组、P_2组和P_1组于缺血前分别经股静脉输注异丙酚10、20、30 mg·kg~(-1)·h-115 min.连续测定Ⅱ导联心电图至再灌注后60 min,并进行心律失常评分.于再灌注60 min时处死大鼠,取左心室缺血区心肌组织,测定心肌细胞膜Na~+-K~+-ATP酶活性、线粒体钙含量和钠泵α_1、α_2、α_3及β_1的mRNA和蛋白表达水平.结果 与C组比较,IR组、P_1组、P_2组和P3组心律失常评分升高,心肌细胞膜Na~+-K~+-ATP酶活性下降,线粒体钙含量升高,钠泵α_1、α_2、α_3及β_1的mRNA和蛋白表达下调(P<0.01).与IR组比较,P1组、P2组和P3组心律失常评分降低,心肌细胞膜Na~+-K~+-ATP酶活性升高,线粒体钙含量降低,钠泵α_1、α_2、α_3及β_1的mRNA和蛋白表达上调,且呈剂量依赖性(P<0.01).P_1组、P_2组和P_3组间心律失常评分、心肌细胞膜Na~+-K~+-ATP酶活性和心肌线粒体钙含量差异无统计学意义(P>0.05).结论 异丙酚减轻大鼠心肌缺血再灌注损伤与上调心肌钠泵的表达,恢复心肌细胞膜Na~+-K~+-ATP酶活性,减轻线粒体钙超载有关.

Effects of propofol on Na~+-K~+-ATPase activity in myocardial cell membrane and intramitochondrial calcium content during myocardial ischemia-reperfusion in rats

Objective To investigate the effects of propofol on Na+-K+-ATPase activity in myocardial cell membrane and intramitochondrial calcium content during myocardial ischemia-reperfusion (IR) in rats. Methods Forty male SD rats weighing 300-350 g were randomly divided into 3 groups (n = g each) : sham operation group (group S), IR group and different doses of propofol groups (group P1-3). Myocardial ischemia was produced by occlusion of left anterior descending branch (LAD) of coronary artery for 30 min followed by 60 min reperfusion in group IR and P1-3. LAD was exposed but not occluded in group S. Propofol was infused via femoral vein at 10, 20 and 30 mg·kg~(-1)·h~(-1) for 15 min before myocardial ischemia in group P1-3 respectively. Lead ⅡECG was continuously monitored and the severity of arrhythmia was quantified using arrhythmia score. The rats were killed and left ventricular myocardial tissues in the ischemic area were removed at 60 min of reperfusion for determination of the activity of Na~+-K~+-ATPase in myocardial cell membrane, intramitochondrial calcium content and α_1, α_2, α_3 and β_1 mRNA and protein expression of sodium pump. Results Compared with group S, arrhythmia scores were significantly increased, Na~+ -K~+ -ATPase activity in myocardial cell membrane was significantly decreased, intramitochondrial calcium content was significantly increased, and α_1, α_2, α_3 and β_1 mRNA and protein expression of sodium pump was down-regulated in group IR and P1-3 (P< 0.01). Compared with group IR, arrhythmia scores were significantly decreased, Na~+-K~+-ATPase activity in myocardial cell membrane was significantly increased, intramitochondrial calcium content was significantly decreased, and α_1 , α_2, α_3 and β_1 mRNA and protein expression of sodium pump was down-regulated in a dose-dependent manner in group IR and P1-3 (P < 0.01). There were no significant differences in arrhythmia scores, Na~+ -K~+-ATPase activity in myocardial cell membrane, intramitochondrial calcium content among the different doses of propefol groups (P> 0.05) .Conclusion Propofol can attenuate IR injury through up-regulation of the expression of sodium pump, recovery of Na~+-K~+-ATPase activity in myocardial cell membrane and reduction in intramitochondrial calcium overload.