Involvement of apoptosis in the cardioprotective effect of volatile anesthetics

细胞凋亡参与挥发性麻醉药的心脏保护作用

• 批准号: 18592210
• 负责人: MIYAMAE Masami
• 金额: $ 2.4万
• 依托单位: Osaka Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18592210/
• 关键词: sevoflurane; apoptosis; Preconditioning; alcohol; Akt; heart; mitochondrial KATP channel; ischemia-reperfusion; heart; Bcl-2; Bax

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

1。抗凋亡激酶是否参与七氟醚的心脏保护作用？已有报道据报道异氟烷诱导的心肌预处理取决于磷脂酰氨基辛醇-3-激酶（PI3K）/akt信号传播，其中心作用是salvage kinvage kinvage kinvage kinvage kinvage kinvage kinvage kinvage。目前尚不清楚该信号级联是否参与了七氟溶液引起的预处理。孤立的灌注豚鼠心脏接受了30分钟的全球缺血和120分钟的再灌注（CTL）。通过在缺血前10分钟（SEVO）的10分钟冲洗（SEVO），通过10分钟的Sevoflurane（1 Mac; 2％）给予Sevoflurane诱导的预处理。通过Western印迹评估了AKT的磷酸化。缺血再灌注后，Sevo具有较高的左心室发育，而舒适性与CTL相比。与CTL相比，SEVO的梗塞大小显着降低。在缺血期间和再灌注后10分钟，AKT磷酸化并未增加，这与发现相反……在异氟烷引起的预处理中先前证明的更多INS。其他再灌注损伤挽救激酶，例如有丝分裂原激活的蛋白激酶/细胞外信号调节激酶（MEK）和细胞外信号调节激酶（ERK），在七氟烷诱导的预处理中可能更重要。2。乙醇和七氟乙烷引起的预处理之间是否存在任何相互作用？我们研究了七氟醚是否增强了乙醇预处理，是否抑制蛋白激酶C（PKC）和线粒体KATP通道是否会减弱这种增强的心脏保护。孤立的灌注豚鼠心脏接受了30分钟的全球缺血和120分钟的再灌注（对照：CTL）。乙醇组（ETOH）在饮用水中接受2.5％的乙醇6周。通过10分钟暴露于乙醇（EtOH+Sevo）或非乙醇（Sevo）心脏中的Sevoflurane（1 Mac; 2％），通过10分钟暴露于Sevoflurane（1 Mac; 2％）。分别用切氏（CHE）和5-羟基苯甲酸酯（5-HD）预处理抑制PKC和线粒体KATP通道。与CTL相比，缺血 - 再灌注后，EtOH，Sevoflurane（Sevo）和EtOH+Sevo组具有较高的LVDP，LVEDP较低。与CTL相比，ETOH和SEVO心脏中的梗塞大小降低。 Sevoflurane进一步降低了EtoH心脏中的基础设施大小。 CHE和5-HD消除了Sevo和EtoH心脏保护性心脏中的心脏保护。 iNOS表达降低，ETOH心脏中的eNOS表达增加。 Sevoflurane增强了常规ETOH消耗引起的心脏预处理。这种效应部分是通过调节PKC和线粒体K_ <ATP>通道来介导的，并且可能通过改变NOS表达的调制。较少的

项目成果

Sevoflurane preconditioning does not diminish phosphorylation of P38MAPK and MAPKAPK2 during sustained ischemia.

七氟烷预处理不会减少持续缺血期间 P38MAPK 和 MAPKAPK2 的磷酸化。

• 发表时间: 2006
• 作者: Uchihashi T;et. al.;高橋 直之;Sun W;Sun W;J Sato;K Kaneyama;Kaneyama K.;Kaneyama K;Kaneyama K;J Sato;K Fujimura;Fujimura K.;K Fujimura;金田 一弘;稲村 吉高;KANEDA K.;金田 一弘;大草 知佳;大草 知佳;OKUSA C.;OKUSA C.;OKUSA C.;SUGIOKA S.
• 通讯作者: SUGIOKA S.

セボフルランによる急性プレコンディショニングの心筋保護効果は1時間以内に消失する

七氟醚急性预处理的心肌保护作用在1小时内消失

• 发表时间: 2007
• 作者: Uchihashi T;et. al.;高橋 直之;Sun W;Sun W;J Sato;K Kaneyama;Kaneyama K.;Kaneyama K;Kaneyama K;J Sato;K Fujimura;Fujimura K.;K Fujimura;金田 一弘;稲村 吉高;KANEDA K.;金田 一弘;大草 知佳
• 通讯作者: 大草 知佳

Involvement of Akt in sevoflurane-induced Attenuation of cardiac ischemia-reperfusion injury

Akt 参与七氟烷诱导的心肌缺血再灌注损伤的减轻

• 发表时间: 2007
• 作者: Uchihashi T;et. al.;高橋 直之;Sun W;Sun W;J Sato;K Kaneyama;Kaneyama K.;Kaneyama K;Kaneyama K;J Sato;K Fujimura;Fujimura K.;K Fujimura;金田 一弘;稲村 吉高;KANEDA K.
• 通讯作者: KANEDA K.

Sevoflurane enhances ethanol-induced cardiac preconditioning through mitochondrial K^<ATP> channels and Protein Kinase C activation in guinea pig hearts

七氟醚通过线粒体 K^<ATP> 通道和蛋白激酶 C 激活增强豚鼠心脏中乙醇诱导的心脏预处理

• 发表时间: 2006
• 作者: Uchihashi T;et. al.;高橋 直之;Sun W;Sun W;J Sato;K Kaneyama;Kaneyama K.;Kaneyama K;Kaneyama K;J Sato;K Fujimura;Fujimura K.;K Fujimura;金田 一弘;稲村 吉高;KANEDA K.;金田 一弘;大草 知佳;大草 知佳;OKUSA C.;OKUSA C.;OKUSA C.;SUGIOKA S.;金田 一弘;KANEDA K.
• 通讯作者: KANEDA K.

Anesthetic preconditoning by 2% sevoflurane is lost within 1 hr after a brief exposure in isolated guinea pig hearts.

麻醉%20预处理%20by%202%%20七氟烷%20is%20lost%20内%201%20hr%20后%20a%20brief%20暴露%20in%20隔离%20几内亚%20猪%20心。

• 发表时间: 2007
• 作者: Uchihashi T;et. al.;高橋 直之;Sun W;Sun W;J Sato;K Kaneyama;Kaneyama K.;Kaneyama K;Kaneyama K;J Sato;K Fujimura;Fujimura K.;K Fujimura;金田 一弘;稲村 吉高;KANEDA K.;金田 一弘;大草 知佳;大草 知佳;OKUSA C.;OKUSA C.
• 通讯作者: OKUSA C.