Takahashi Yosuke, Takemura Shigekazu, Minamiyama Yukiko, Shibata Tohihiko, Hirai Hidekazu, Sasaki Yasuyuki, Sakaguchi Masanori, Suehiro Shigefumi
Department of Cardiovascular Surgery, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka, Japan.
Free Radic Res. 2007 Jul;41(7):757-69. doi: 10.1080/10715760701338810.
Landiolol, a highly cardioselective beta1-blocker, has cardioprotective effects against ischemia-reperfusion injury, although the precise mechanism is still unclear. The aim of this study was to clarify the cardioprotective mechanism of landiolol. Experiments were performed on Langendorff-perfused rat hearts undergoing 20 min stabilization, and 45 min of ischemia followed by 60 min of reperfusion. Various drugs with or without landiolol (100 microM) were administered before ischemia for 20 min. Preischemic administration of landiolol reduced cardiac cellular damage and improved the recovery of cardiac function by about 40%. The alpha1 blocker prazosin, the protein kinase C (PKC) inhibitor chelerythrine or the K(ATP) channel blocker glibenclamide, but not the selective mitochondrial K(ATP) channel blocker 5-hydroxydecanoate abrogated the cardioprotective effect induced by landiolol. Following landiolol pretreatment the activation of PKCepsilon and heat shock protein 27 were significantly higher than that in control. These data indicate that preischemic application of landiolol induces cardioprotective effects through PKCepsilon-mediated pathway, similar to that afforded by ischemic preconditioning.
兰地洛尔是一种高度心脏选择性β1受体阻滞剂,对缺血再灌注损伤具有心脏保护作用,尽管其确切机制仍不清楚。本研究的目的是阐明兰地洛尔的心脏保护机制。实验在Langendorff灌注的大鼠心脏上进行,先稳定20分钟,然后缺血45分钟,再灌注60分钟。在缺血前20分钟给予各种含或不含兰地洛尔(100微摩尔)的药物。缺血前给予兰地洛尔可减少心肌细胞损伤,并使心功能恢复提高约40%。α1受体阻滞剂哌唑嗪、蛋白激酶C(PKC)抑制剂白屈菜红碱或K(ATP)通道阻滞剂格列本脲可消除兰地洛尔诱导的心脏保护作用,但选择性线粒体K(ATP)通道阻滞剂5-羟基癸酸不能消除。兰地洛尔预处理后,PKCε和热休克蛋白27的激活明显高于对照组。这些数据表明,缺血前应用兰地洛尔通过PKCε介导的途径诱导心脏保护作用,类似于缺血预处理所提供的保护作用。