[丙泊酚对大鼠心肌缺血再灌注损伤具有缺血后适应作用]

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

作者信息

Wang Hai-Yun, Wang Guo-Lin, Yu Yong-Hao, Chen Xing-Yun, Wang Ying

机构信息

Department of Anesthesiology, General Hospital, Tianjin Medical University, Tianjin 300052, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2009 Jan 6;89(1):54-8.

PMID:19489246

Abstract

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 min. 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 TTC 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 apoptotic 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 apoptotic 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.

摘要

目的

探讨早期再灌注期间输注丙泊酚是否能对大鼠心肌缺血-再灌注损伤产生缺血后处理（I-postC）作用。

方法

将60只成年大鼠随机分为5组（每组n = 12）：假手术组（S组）；生理盐水组（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）。结扎左冠状动脉前降支60分钟，再灌注120分钟。在再灌注前3分钟至再灌注后5分钟，分别静脉输注生理盐水、丙泊酚1 mg/kg、2 mg/kg或5 mg/kg（丙泊酚用生理盐水等体积稀释至2.5 ml）。取心脏用于测定：（1）危险区面积和梗死面积大小（伊文思蓝和TTC染色）；（2）Caspase-3表达（免疫组织化学染色）；（3）凋亡心肌细胞百分比（流式细胞术）；（4）磷酸化Akt水平（蛋白质印迹法）。

结果

与C组相比[危险区面积大小（41.5±1.0）%，梗死面积大小（45.5±1.0）%，Caspase-3表达（5.87±0.29），凋亡心肌细胞百分比（26.8±1.3）%，磷酸化Akt水平（10.8±1.9）%]，丙泊酚1 mg/kg和2 mg/kg组显著减小了危险区面积和梗死面积大小[危险区面积大小（38.3±1.0）%和（37.3±1.2）%；梗死面积大小（33.8±1.2）%和（30.2±1.7）%，P < 0.05]，抑制了Caspase-3表达（1.50±0.36和1.48±0.30，P < 0.05），降低了凋亡心肌细胞百分比[（16.3±1.2）%和（16.5±1.0）%，P < 0.05]，并促进了Akt磷酸化[（68.7±4.0）%和（58.3±2.8）%，P < 0.05]。