七氟醚后处理仅 5 分钟即可最大程度激活 Akt 并对再灌注损伤发挥心脏保护作用。
Activation of Akt and cardioprotection against reperfusion injury are maximal with only five minutes of sevoflurane postconditioning in isolated rat hearts.
机构信息
Department of Anesthesiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
出版信息
J Zhejiang Univ Sci B. 2013 Jun;14(6):511-7. doi: 10.1631/jzus.B1200195.
It had been proved that administration of sevoflurane for the first two minutes of reperfusion effectively protects the heart against reperfusion injury in rats in vivo. Our aim was to investigate the duration of effective sevoflurane administration and its underlying mechanism in isolated rat hearts exposed to global ischemia/reperfusion (I/R) injury. Adult male Sprague-Dawley rats were randomly divided into six groups (n=12): a sham-operation group, an I/R group, and four sevoflurane postconditioning groups (S2, S5, S10, and S15). In the S2, S5, S10, and S15 groups, the duration times of sevoflurane administration were 2, 5, 10, and 15 min after the onset of reperfusion, respectively. The isolated rat hearts were mounted on the Langendorff system, and after a period of equilibrium were subjected to 40 min global ischemia and 120 min reperfusion. Left ventricular (LV) hemodynamic parameters were monitored throughout each experiment and the data at 30 min of equilibrium and 30, 60, 90, and 120 min of reperfusion were analyzed. Myocardial infarct size at the end of reperfusion (n=7 in each group) and the expression of myocardial phosphorylated Akt (p-Akt) after 15-min reperfusion were determined in a duplicate set of six groups of rat hearts (n=5 in each group). Compared with the I/R group, the S5, S10, and S15 groups had significantly improved left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), and the maximal rate of rise or fall of the LV pressure (±dP/dtmax), and decreased myocardial infarct size (P<0.05), but not the S2 group. After 15 min of reperfusion, the expression of p-Akt was markedly up-regulated in the S5, S10, and S15 groups compared with that in the I/R group (P<0.05), but not in the S2 group. Sevoflurane postconditioning for 5 min was sufficient to activate Akt and exert maximal cardioprotection against I/R injury in isolated rat hearts.
已有研究证实，七氟醚在再灌注的前 2 分钟给药可有效减轻大鼠在体心脏再灌注损伤。本研究旨在探讨七氟醚后处理对离体大鼠心脏缺血/再灌注（I/R）损伤的有效作用时间及其可能的作用机制。成年雄性 Sprague-Dawley 大鼠随机分为 6 组（n=12）：假手术组、I/R 组和 4 个七氟醚后处理组（S2、S5、S10 和 S15）。在 S2、S5、S10 和 S15 组中，七氟醚的给药时间分别为再灌注开始后 2、5、10 和 15 min。将离体心脏置于 Langendorff 系统上，经过一段平衡期后进行 40 min 缺血和 120 min 再灌注。整个实验过程中监测左心室（LV）血流动力学参数，并分析平衡 30 min 以及再灌注 30、60、90 和 120 min 时的数据。再灌注结束时（每组 n=7）测定心肌梗死面积，并在另一组 6 只大鼠心脏（每组 n=5）中检测再灌注 15 min 后心肌磷酸化 Akt（p-Akt）的表达。与 I/R 组相比，S5、S10 和 S15 组左心室舒张末期压（LVEDP）、左心室发展压（LVDP）和左心室压力最大上升或下降速率（±dP/dtmax）显著改善，心肌梗死面积减小（P<0.05），但 S2 组没有明显变化。再灌注 15 min 后，S5、S10 和 S15 组 p-Akt 的表达明显高于 I/R 组（P<0.05），但 S2 组没有明显变化。七氟醚后处理 5 min 即可激活 Akt，对离体大鼠心脏 I/R 损伤发挥最大的心脏保护作用。
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