性别因素对七氟醚后处理减轻大鼠离体心肌缺血再灌注损伤的影响

目的 探讨性别因素对七氟醚后处理减轻大鼠离体心肌缺血再灌注损伤的影响.方法 SD大鼠60只,雄雌各半,2月龄,雄性大鼠随机分为对照组(MC组)和七氟醚后处理组(MS组),雌性大鼠随机分为对照组(FC组)和七氟醚后处理组(FS组),每组15只.建立大鼠离体心脏灌注模型,采用全心缺血40 min,再灌注2 h的方法制备缺血再灌注模型.对照组心脏再灌注时给予含氧K-H缓冲液,七氟醚后处理组在复灌的前10min灌注经3%七氟醚饱和的含氧K-H缓冲液,余110 min灌注含氧K-H缓冲液.于缺血前、再灌注期间记录HR、左心室舒张末压(LVEDP)和左心室发展压(LVDP),再灌注5 min时测定冠状动脉流出液LDH活性和心肌梗死面积,再灌注10 min时测定心肌总蛋白激酶B(t-Akt)、磷酸化蛋白激酶B(p-Akt)的表达,计算p-Akt与t-Akt比值(p-Akt/t-Akt).结果 与MC组比较,MS组和FC组LVDP升高,LVEDP降低,冠状动脉流出液LDH活性降低,心肌梗死面积减小,心肌p-Akt表达上调,p-Akt/t-Akt升高(P＜0.05);与MS组比较,FS组LVDP降低,LVEDP和冠状动脉流出液LDH活性升高,心肌梗死面积增大(P＜0.05);FC组和FS组LVDP和LVEDP比较差异无统计学意义(P＞0.05).结论 七氟醚后处理减轻大鼠离体心肌缺血再灌注损伤存在性别差异,对雄性大鼠的心肌保护作用强于雌性大鼠,该差异可能与心肌Akt的活化水平有关.

Effect of gender factors on reduction of ischemia-reperfusion injury by sevoflurane postconditioning in isolated rat cardiomyocytes

Objective To investigate the effect of gender factors on the reduction of ischemia-reperfusion (I/R) injury by sevoflurane postconditioning in isolated rat cardiomyocytes. Methods Sixty 2-month-old SD rats (30 male, 30 female) were used in this study. Male rats were randomly assigned into 2 groups (n = 15 each):control group (group MC) and sevoflurane postconditioning group (group MS). Female rats were also randomly assigned into 2 groups (n= 15 each): control group (group FC) and sevoflurane postconditioning group (group FS).The rats were anesthetized with intraperitoneal pentobarbital 60 mg/kg. Their hearts were excised and perfused in a Langendorff apparatus with K-H solution saturated with 95% O2-5% CO2 at 37 ℃. I/R was produced by 40 min of global ischemia followed by 120 min of reperfusion. Control groups received perfusion with K-H solution saturated with O2 . Sevofiurane postconditioning groups received 10 min of perfusion with K-H solution saturated with 3%sevoflurane and O2 and then 110 min of perfusion with K-H solution saturated with O2 . HR, left ventricular enddiastolic pressure (LVEDP) and left ventricular developed pressure (LVDP) were measured before ischemia and during reperfusion. Coronary effluent was collected at 5 min of reperfusion for determination of LDH activity and infarct size. The total Akt (t-Akt) and phosphorylated Akt (p-Akt) expression in cardiomyocytes was detected. The ratio of p-Akt to t-Akt (p-Akt/t-Akt) was calculated. Results LVDP, p-Akt expression and p-Akt/t-Akt were significantly higher, LVEDP and LDH activity were significantly lower, and the infarct size was smaller in group MS and FC than in group MC (P ＜ 0.05). LVDP was significantly lower, LVEDP and LDH activity were significantly higher, and the infarct size was larger in group FS than in group MS. There was no significant difference in LVDP and LVEDP between group FC and FS (P ＞ 0.05). Conclusion There are gender differences in the reduction of I/R injury by sevoflurane postconditioning in isolated rat cardiomyocyes, the protective effect is stronger in male rats than in female rats, and the differences may be related to the activation of Akt.