摘要
Objective：To investigate the antioxidative effect and mechanism of luteolin on rat cardiomyocytes and isolated hearts fol owed by simulated ischemia/reperfusion（SI/R） injury. Methods：The left ventricular cardiomyocytes and the isolated hearts from adult rats were subjected to SI/R injury. The experiment groups included control, SI/R, luteolin ＋ SI/R（Lut ＋ SI/R）, vitamin E（Vit E） ＋ SI/R, and LY294002 ＋ luteolin ＋ SI/R（LY ＋ Lut ＋ SI/R） groups. Cell viability, shortening amplitude, lactate dehydrogenase（LDH） release, superoxide dismutase（SOD） activity, the production of reactive oxygen species（ROS） and malondialdehyde（MDA）, expression levels of Akt, phosphorylated Akt, NOX2（gp91phox）, NOX2 m RNA, mitogen-activated protein kinase（p38 MAPK） and phosphorylated p38 MAPK were al measured after 3-h simulated ischemia and 2-h simulated reperfusion procedure in cardiomyocytes. Vit E was used as a standard control. The contractile function of isolated hearts was further observed after they were subjected to 30-min global ischemia and 120-min reperfusion. Results：Pretreatment with 8-μmol/L luteolin substantially increased cel viability and shortening amplitude, while reducing evidence of oxidative stress-induced damage in the cel s. In addition, the expression of NOX2, NOX2 m RNA and phosphorylation of p38 MAPK were al downregulated. Furthermore, pretreatment with 40-μmol/L luteolin improved the recovery of myocardial contractile function fol owing SI/R-induced injury, and luteolin markedly increased phosphorylation of Akt. However, all of the above effects were partially inhibited by the phosphatidylinositol 3-kinase（PI3K） inhibitor, LY294002. Conclusions：Luteolin prevents SI/R-induced myocardial damage by reducing oxidative stress-induced injury in isolated rat hearts and cardiomyocytes, and the cardioprotection induced by luteolin was partial y mediated by the PI3K/Akt pathway.
Objective：To investigate the antioxidative effect and mechanism of luteolin on rat cardiomyocytes and isolated hearts fol owed by simulated ischemia/reperfusion（SI/R） injury. Methods：The left ventricular cardiomyocytes and the isolated hearts from adult rats were subjected to SI/R injury. The experiment groups included control, SI/R, luteolin ＋ SI/R（Lut ＋ SI/R）, vitamin E（Vit E） ＋ SI/R, and LY294002 ＋ luteolin ＋ SI/R（LY ＋ Lut ＋ SI/R） groups. Cell viability, shortening amplitude, lactate dehydrogenase（LDH） release, superoxide dismutase（SOD） activity, the production of reactive oxygen species（ROS） and malondialdehyde（MDA）, expression levels of Akt, phosphorylated Akt, NOX2（gp91phox）, NOX2 m RNA, mitogen-activated protein kinase（p38 MAPK） and phosphorylated p38 MAPK were al measured after 3-h simulated ischemia and 2-h simulated reperfusion procedure in cardiomyocytes. Vit E was used as a standard control. The contractile function of isolated hearts was further observed after they were subjected to 30-min global ischemia and 120-min reperfusion. Results：Pretreatment with 8-μmol/L luteolin substantially increased cel viability and shortening amplitude, while reducing evidence of oxidative stress-induced damage in the cel s. In addition, the expression of NOX2, NOX2 m RNA and phosphorylation of p38 MAPK were al downregulated. Furthermore, pretreatment with 40-μmol/L luteolin improved the recovery of myocardial contractile function fol owing SI/R-induced injury, and luteolin markedly increased phosphorylation of Akt. However, all of the above effects were partially inhibited by the phosphatidylinositol 3-kinase（PI3K） inhibitor, LY294002. Conclusions：Luteolin prevents SI/R-induced myocardial damage by reducing oxidative stress-induced injury in isolated rat hearts and cardiomyocytes, and the cardioprotection induced by luteolin was partial y mediated by the PI3K/Akt pathway.
基金
Supported by the Academic Degrees Committee and the Department of Education of Jiangsu Province(No.CXLX11-0732)
