title: JNK/PI3K/Akt signaling pathway is involved in myocardial ischemia/reperfusion injury in diabetic rats: effects of salvianolic acid A intervention.
abstract: Recent studies have demonstrated that diabetes impairs the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) pathway, while insulin resistance syndrome has been associated with alterations of this pathway in diabetic rats after ischemia/reperfusion (I/R), and activation of C-jun N-terminal kinase (JNK) is involved. The present study was designed to investigate whether inhibiting JNK activity would partially restore the PI3K/Akt signaling pathway and protect against myocardial I/R injury in diabetic rats, and to explore the effect of intervention with salvianolic acid A (Sal A). The inhibitor of JNK (SP600125) and Sal A were used in type 2 diabetic (T2D) rats, outcome measures included heart hemodynamic data, myocardial infarct size, the release of lactate dehydrogenase (LDH), SERCA2a activity, cardiomyocyte apotosis, expression levels of Bcl-2, Bax and cleaved caspase-3, and the phosphorylation status of Akt and JNK. The p-Akt levels were increased after myocardial I/R in non-diabetic rats, while there was no change in diabetic rats. Pretreatment with the SP600125 and Sal A decreased the p-JNK levels and increased the p-Akt levels in diabetic rats with I/R, and heart hemodynamic data improved, infarct size and LDH release decreased, SERCA2a activity increased, Bax and cleaved caspase-3 expression levels decreased, and the expression of Bcl-2 and the Bcl-2/Bax ratio increased. Our results suggest that the JNK/PI3K/Akt signaling pathway is involved in myocardial I/R injury in diabetic rats and Sal A exerts an anti-apoptotic effect and improves cardiac function following I/R injury through the JNK/PI3K/Akt signaling pathway in this model.
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical University 84 West Huaihai Road, Xuzhou, Jiangsu, People's Republic of China.
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Affiliated Hospital of Xuzhou Medical University 99 West Huaihai Road, Xuzhou 221002, Jiangsu, People's Republic of China.
authors.forename: Tongda
authors.initials: T
authors.lastname: Xu
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical University84 West Huaihai Road, Xuzhou, Jiangsu, People's Republic of China; Department of Cardiology, Affiliated Hospital of Xuzhou Medical University99 West Huaihai Road, Xuzhou 221002, Jiangsu, People's Republic of China.
authors.forename: Dongye
authors.initials: D
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical University 84 West Huaihai Road, Xuzhou, Jiangsu, People's Republic of China.
authors.forename: Defeng
authors.initials: D
authors.lastname: Pan
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical University 84 West Huaihai Road, Xuzhou, Jiangsu, People's Republic of China.
authors.forename: Pei
authors.initials: P
authors.lastname: Wu
authors.affiliation: Department of Cardiology, Affiliated Hospital of Xuzhou Medical University 99 West Huaihai Road, Xuzhou 221002, Jiangsu, People's Republic of China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Cardiology, Affiliated Hospital of Xuzhou Medical University 99 West Huaihai Road, Xuzhou 221002, Jiangsu, People's Republic of China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical University 84 West Huaihai Road, Xuzhou, Jiangsu, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
keywords: Diabetic rats; JNK; PI3K/Akt signaling pathway; Sal A; ischemia/reperfusion