Involvement of apoptosis in the cardioprotective effect of volatile anesthetics

1.抗凋亡蛋白Akt是否参与了七氟烷的心肌保护作用？已有研究表明，异氟醚诱导的心肌预适应依赖于磷脂酰肌醇-3-激酶(PI3K)/Akt信号通路，而磷脂酰肌醇-3-激酶(PI3K)/Akt信号转导通路在再灌注损伤挽救激酶级联反应中起中心作用。目前尚不清楚这一信号级联是否参与了七氟醚诱导的预适应。灌流豚鼠离体心30min，再灌流120min(CTL)。七氟醚(1MAC；2%)给药10min，于缺血前冲洗10min，可诱导七氟醚预适应。蛋白印迹法检测Akt蛋白的磷酸化。缺血再灌注后，SEVO较CTL有更高的左心室发育和更低的舒张末压力。与CTL相比，SEVO组的梗塞面积显著缩小。在缺血和再灌流10min后，AKT的磷酸化水平没有增加，这与Find…相反在异氟醚诱导的预适应中，有更多的ING被证实。结论：1.在七氟醚诱导的预适应过程中，丝裂原活化蛋白激酶/细胞外信号调节激酶(MEK)和细胞外信号调节激酶(ERK)等抢救性信号通路在再灌注损伤中可能发挥更重要的作用。在乙醇和七氟醚诱导的预适应之间是否存在相互作用？我们研究了七氟醚是否增强了乙醇预适应，以及蛋白激酶C(PKC)和线粒体KATP通道的抑制是否减弱了这种增强的心脏保护作用。体外灌流豚鼠心脏，全心缺血30min，再灌注120min(对照组：CTL)。乙醇组(Etoh)在饮用水中加入2.5%乙醇，连续6周。麻醉预适应由七氟醚(1MAC；2%)在乙醇(Etoh+Sevo)或非乙醇(Sevo)心脏中暴露10min引起。白屈菜红碱(ChE)和5-羟基癸酸(5-HD)分别抑制PKC通道和线粒体KATP通道。缺血再灌注后，无水乙醇、七氟醚(Sevo)和无水乙醇+七氟醚(SEVO)组较CTL组LVdP升高，LVEDP降低。与CTL相比，Etoh和Sevo组心肌梗死面积缩小。七氟醚进一步缩小了无水乙醇心脏的梗塞面积。CHE和5-HD取消了Sevo和Etoh心脏保护心脏的心脏保护作用。无水乙醇心脏iNOS表达减少，eNOS表达增加。七氟醚可增强常规乙醇消耗诱导的心脏预适应。这种作用部分是通过调节PKC和线粒体K_(t；t；ATP&gt)通道，以及可能通过改变NOS的表达来实现的。较少

1. Is Akt, antiapoptotic kinase, involved in the cardioprotective effect of sevoflurane ?It has been reported that isoflurane-induced myocardial preconditioning is dependent on phosphatidylinositol-3-kinase (PI3K)/Akt signaling which plays a central role of reperfusion injury salvage kinase cascade. It remains unclear whether this signaling cascade is involved in sevoflurane-induced preconditioning. Isolated perfused guinea pig hearts underwent 30 min global ischemia and 120 min reperfusion (CTL). Sevoflurane-induced preconditioning was elicited by administration of 10 min of sevoflurane (1 MAC; 2%) with 10 min washout before ischemia (SEVO). Phosphorylation of Akt was assessed by western blot. After ischemia-reperfusion, SEVO had higher left ventricular developed and lower end-diastolic pressure versus CTL. Infarct size was significantly reduced in SEVO compared to CTL. Akt phosphorylation was not increased during ischemia and 10 min after reperfusion, which is in contrast to the find … More ings previously demonstrated in isoflurane-induced preconditioning. Other reperfusion injury salvage kinases such as mitogen-activated protein kinase/extracellular signal-regulated kinases (MEK) and extra-cellular signal-regulated kinase (ERK) may be more important in sevoflurane-induced preconditioning.2. Is there any interaction between ethanol-and sevoflurane-induced preconditioning ?We investigated whether sevoflurane enhances ethanol preconditioning and whether inhibition of protein kinase C (PKC) and mitochondrial KATP channels attenuated this enhanced cardioprotection. Isolated perfused guinea pig hearts underwent 30 min global ischemia and 120 min reperfusion (Control: CTL). The ethanol group (EtOH) received 2.5% ethanol in their drinking water for 6 weeks. Anesthetic preconditioning was elicited by 10 min exposure to sevoflurane (1 MAC; 2%) in ethanol (EtOH+SEVO) or non-ethanol (SEVO) hearts. PKC and mitochondrial KATP channels were inhibited with chelerythrine (CHE) and 5-hydroxydecanoate (5-HD) pretreatment, respectively. After ischemia-reperfusion, EtOH, sevoflurane (SEVO), and EtOH+SEVO groups had higher LVDP and lower LVEDP compared with CTL. Infarct size was reduced in EtOH and SEVO hearts compared with CTL. Sevoflurane further reduced infarct size in EtOH hearts. CHE and 5-HD abolished cardioprotection in both SEVO and EtOH cardioprotected hearts. iNOS expression was reduced and eNOS expression was increased in EtOH hearts. Sevoflurane enhances cardiac preconditioning induced by regular EtOH consumption. This effect is mediated in part by modulation of PKC and mitochondrial K_<ATP> channels, and possibly by altered modulation of NOS expression. Less