丙泊酚对大鼠心肌缺血后处理的作用

目的 探讨不同剂量丙泊酚缺血后处理对大鼠心肌缺血/再灌注损伤的作用.方法 制备大鼠心肌缺血/再灌注损伤模型,结扎冠状动脉左前降支60 min,再灌注120 min.随机分为假手术组(S组)、生理盐水对照组(C组)、丙泊酚1 mg/kg组(P1组)、丙泊酚2 mg/kg组(P2组)、丙泊酚5 mg/kg组(P3组),除S组其余各组所用药物均以生理盐水稀释至2.5 ml,于再灌注前3 min经股静脉匀速输注至再灌注后5 min,测定心肌危险区面积和梗死区面积;采用免疫组化方法 检测心肌组织Caspase-3的表达;应用流式细胞仪检测心肌细胞凋亡率;运用Western印迹方法 测定Akt磷酸化水平.结果 与C组[危险区面积(41.5±1.0)%,梗死区面积(45.5±1.0)%,Caspase-3表达5.87±0.29,心肌细胞凋亡率(26.8±1.3)%,Akt磷酸化(10.8±1.9)%]相比,P1组和P2组大鼠危险区面积和梗死区面积明显减小[危险区面积(38.3±1.0)%和(37.3±1.2)%;梗死区面积(33.8±1.2)%和(30.2±1.7)%,均P<0.05];Caspase-3表达降低(1.50±0.36和1.48±0.30,均P<0.05);心肌细胞凋亡率下降[(16.3±1.2)%和(16.5±1.0)%,均P<0.05];而Akt磷酸化水平明显升高[(68.7±4.0)%和(58.3±2.8)%,均P<0.05].结论 丙泊酚1 mg/kg和2 mg/kg通过促进Akt磷酸化发挥I-postC保护作用.

Propofol provides ischemic postconditioning on myocardial ischemia-reperfusion injury in rats

Objective To investigate whether the infusion of propofol during early reperfusion provides ischemic postconditioning (I-postC) on myocardial ischemia-reperfusion injury in rats. Methods Sixty adult rats were randomly divided into 5 groups (n = 12 each) : sham operation (group S) ; normal saline (group C); propofol 1 mg/kg (group P1); propofol 2 mg/kg (group P2); propofol 5 mg/kg (group P3). The left anterior descending coronary artery (LAD) was occluded for 60 min and reperfused for 120 mira Normal saline, propofol 1 mg/kg, 2 mg/kg or 5 mg/kg (propofol diluted to 2.5 ml with normal saline equally) were intravenously infused 3 min before reperfusion until 5 min after reperfusion. The heart were obtained for determination of (1) the size of area at risk and infarct size (Evans Blue and Trc staining) ; (2) expression of Caspase-3 (immunohistochemistry staining) ; (3) percentage of apoptotic cardiomyocytes (flow cytometry) ; (4) levels of phosphorylated Akt (Western blot). Results Compared with group C [size of area at risk (41.5±1.0) %, infarct size (45.5±1.0) %, expression of caspase-3 (5.87± 0.29), percentage of apeptotic cardiomyocytes (26.8±1.3)%, level of phosphorylated Akt (10.8± 1.9)%], propofol 1 mg/kg and 2 mg/kg significantly reduced the size of area at risk and infarct size [size of area at risk (38.3±1.0) % and (37.3±1.2) % ; infarct size (33.8±1.2) % and (30.2±1.7) %, P < 0.05], inhibited the expression of caspase-3 (1.50±0.36 and 1.48±0.30, P < 0.05), decreased the percentage of apeptotic cardiomyocytes [(16.3±1.2) % and (16.5±1.0) %, P < 0.05] and promoted the phosphorylation of Akt [(68.7±4.0) % and (58.3±2.8) %, P < 0.05]. Conclusion Propofol 1 mg/kg and 2 mg/kg can provide I-postC to myocardial ischemia-reperfusion injury in rats by activation of Akt pathway.