Activation of Akt and cardioprotection against reperfusion injury are maximal with only five minutes of sevoflurane postconditioning in isolated rat hearts
Activation of Akt and cardioprotection against reperfusion injury are maximal with only five minutes of sevoflurane postconditioning in isolated rat hearts
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在离体大鼠心脏中仅进行五分钟的七氟醚后处理，Akt 的激活和针对再灌注损伤的心脏保护作用就达到最大
DOI：
10.1631/jzus.b1200195
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发表时间：
2013-06-01
影响因子：
5.1
通讯作者：
Yan, Min
中科院分区：
文献类型：
--
作者：
Yao, Yuan-yuan;Zhu, Man-hua;Yan, Min
体内实验证明，再灌注前2分钟给予七氟醚可有效保护大鼠心脏免受再灌注损伤。我们的目的是研究七氟醚有效给药的持续时间及其在暴露于整体缺血/再灌注（I/R）损伤的离体大鼠心脏中的潜在机制。成年雄性Sprague-Dawley大鼠被随机分为六组（n=12）：假手术组、I/R组和四个七氟烷后处理组（S2、S5、S10和S15）。在S2、S5、S10和S15组中，七氟醚给药的持续时间分别为再灌注开始后2、5、10和15分钟。将离体大鼠心脏安装在Langendorff系统上，平衡一段时间后进行40分钟的整体缺血和120分钟的再灌注。在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 分钟以及再灌注 30、60、90 和 120 分钟的数据。在六组大鼠心脏（每组 n=5）中测定再灌注结束时的心肌梗死面积（每组 n=7）和再灌注 15 分钟后心肌磷酸化 Akt（p-Akt）的表达。与I/R组相比，S5、S10、S15组左心室舒张末压（LVEDP）、左心室展开压（LVDP）、左心室压力最大升降速率（±dP/dtmax）均显着改善，心肌梗死面积明显减小（P<0.05），而S2组则无显着性差异。再灌注15 min后，S5、S10、S15组p-Akt表达较I/R组明显上调（P<0.05），而S2组无此变化。七氟烷后处理 5 分钟足以激活 Akt，并对离体大鼠心脏发挥最大的心脏保护作用以抵抗 I/R 损伤。
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.