Yamada Mariko, Nakadate Yosuke, Omiya Keisuke, Oguchi Takeshi, Abe Masako, Matsukawa Takashi
Department of Anesthesiology, University of Tsukuba Hospital, 2-1-1 Amakuba, Tsukuba, Ibaraki 305-8576, Japan.
Department of Anesthesiology, University of Tsukuba Hospital, 2-1-1 Amakuba, Tsukuba, Ibaraki 305-8576, Japan; Department of Anesthesiology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan.
Steroids. 2025 Jan;213:109542. doi: 10.1016/j.steroids.2024.109542. Epub 2024 Nov 28.
S-equol, an isoflavone metabolite with high estrogenic activity, exhibits organ-protective effects via the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. While estrogen has cardioprotective effects against ischemia-reperfusion injury, whether S-equol shares this capability remains uncertain. This study aimed to assess the cardioprotective effects of S-equol on stunned myocardium using an isolated rat heart model and investigate the involvement of PI3K/Akt signaling pathway.
Male rat hearts were perfused using the Langendorff system and divided into four groups: 1) modified Krebs-Henseleit (KH) buffer containing 1 μmol/L S-equol (EQ); 2) KH buffer (Cont); 3) KH buffer supplemented with 1 μmol/L S-equol and 100 nmol/L wortmannin (a specific PI3K inhibitor) (EQW); or 4) KH buffer containing wortmannin (ContW). After stabilization, each group was perfused for 20 min before undergoing 7.5 min of no-flow ischemia, followed by 20 min reperfusion. The primary outcome was the maximum left ventricular derivative of pressure development (left ventricle [LV] dP/dt max)after 20 min of reperfusion. Myocardial Akt and glycogen synthase kinase-3 beta (GSK-3β) were assayed using western blotting.
LV dP/dt max was greater in the EQ group than that in the Cont group after 15 and 20 min of reperfusion; however, this effect was attenuated in the presence of PI3K inhibitors. S-equol treatment increased Akt and suppressed GSK-3β expression in the EQ group compared to that in the Cont group. However, these effects were not observed in the presence of wortmannin.
S-equol exerts a protective effect against myocardial ischemia-reperfusion injury, possibly by activating PI3K/Akt signaling.
S-雌马酚是一种具有高雌激素活性的异黄酮代谢产物，通过磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/Akt）信号通路发挥器官保护作用。虽然雌激素对缺血再灌注损伤具有心脏保护作用，但S-雌马酚是否具有此能力仍不确定。本研究旨在使用离体大鼠心脏模型评估S-雌马酚对顿抑心肌的心脏保护作用，并研究PI3K/Akt信号通路的参与情况。
采用Langendorff系统灌注雄性大鼠心脏，并分为四组：1）含1 μmol/L S-雌马酚（EQ）的改良Krebs-Henseleit（KH）缓冲液；2）KH缓冲液（对照）；3）补充有1 μmol/L S-雌马酚和100 nmol/L渥曼青霉素（一种特异性PI3K抑制剂）的KH缓冲液（EQW）；或4）含渥曼青霉素的KH缓冲液（对照W）。稳定后，每组先灌注20分钟，然后进行7.5分钟无血流缺血，随后再灌注20分钟。主要观察指标是再灌注20分钟后的最大左心室压力上升速率（左心室[LV] dP/dt max）。采用蛋白质印迹法检测心肌Akt和糖原合酶激酶-3β（GSK-3β）。
再灌注15分钟和20分钟后，EQ组的LV dP/dt max高于对照组；然而，在存在PI3K抑制剂的情况下，这种作用减弱。与对照组相比，S-雌马酚处理使EQ组的Akt增加，GSK-3β表达受到抑制。然而，在存在渥曼青霉素的情况下未观察到这些作用。
S-雌马酚对心肌缺血再灌注损伤具有保护作用，可能是通过激活PI3K/Akt信号通路实现的。
