Luteolin Inhibits Apoptosis and Improves Cardiomyocyte Contractile Function through the PI3K/Akt Pathway in Simulated Ischemia/Reperfusion
Luteolin Inhibits Apoptosis and Improves Cardiomyocyte Contractile Function through the PI3K/Akt Pathway in Simulated Ischemia/Reperfusion
复制标题
DOI：
10.1159/000330068
复制
发表时间：
2011-01-01
期刊：
影响因子：
3.1
通讯作者：
Sun, Hong
中科院分区：
文献类型：
--
作者：
Fang, Fang;Li, Dongye;Sun, Hong
木犀草素是一种天然存在的多酚类黄酮，具有心肌保护作用。然而，其机制尚未完全阐明。在本研究中，我们研究了毛地黄黄酮预处理是否与大鼠缺血/再灌注（I/R）模型的心脏保护作用有关。木犀草素不仅能明显恢复心肌收缩力，而且能减少心肌梗死面积和乳酸脱氢酶漏出。此外，毛地黄黄酮预处理可显著改善模拟缺血/再灌注（SI/R）条件下心肌细胞的缩短幅度，降低凋亡率，上调Bcl-2表达，下调Bax表达，升高Bcl-2/Bax比值。此外，毛地黄黄酮预处理增加了SI/R后蛋白激酶B（Akt）磷酸化、受磷蛋白磷酸化和肌浆网钙ATP酶的表达。磷脂酰肌醇3-激酶（PI 3 K）/Akt信号通路是细胞内最重要的生存信号通路之一。为了确定木犀草素诱导的心脏保护作用是否由PI 3 K/Akt通路介导，我们利用PI 3 K抑制剂LY 294002。抑制Akt活性可显着消除毛地黄黄酮诱导的SI/R心肌细胞正性收缩和细胞凋亡抑制。这些结果表明，毛地黄黄酮至少部分通过SI/R中的PI 3 K/Akt通路抑制细胞凋亡并改善心肌细胞收缩功能。版权所有（C）2011 S. Karger AG，巴塞尔
Luteolin, a naturally occurring polyphenol flavonoid, has demonstrated to exert myocardial protection effects. However, the mechanisms have not been fully elucidated. In the present study, we investigated whether luteolin pretreatment was associated with cardioprotection in a rat ischemia/reperfusion (I/R) model. Luteolin significantly not only restored contractility of the left ventricle, but also reduced the infarct size and lactate dehydrogenase leakage during I/R. In addition, luteolin pretreatment significantly improved cardiomyocyte shortening amplitude, decreased the apoptotic rate, upregulated Bcl-2 expression, downregulated Bax expression and raised the Bcl-2/Bax ratio under a simulated ischemia/reperfusion (SI/R) condition. Moreover, luteolin pretreatment increased protein kinase B (Akt) phosphorylation, phospholamban phosphorylation and the expression of sarcoplasmic reticulum calcium ATPase following SI/R. The phosphoinositide 3-kinase (PI3K)/Akt pathway is one of the most important intracellular survival signal pathways. To determine whether luteolin-induced cardioprotection was mediated by the PI3K/Akt pathway, we utilized the PI3K inhibitor LY294002. Inhibition of Akt activity markedly abolished luteolin-induced positive contraction and inhibition of apoptosis in SI/R cardiomyocytes. These results showed that luteolin inhibits apoptosis and improves cardiomyocyte contractile function at least partly through the PI3K/Akt pathway in SI/R. Copyright (C) 2011 S. Karger AG, Basel