icatibant and tanshinone

Diabetic cardiomyopathy, characterized by myocardial structural and functional changes, is a specific cardiomyopathy develops in patients with diabetes mellitus. The present study was to investigate the role of kinin B2 receptor-Akt-glycogen synthase kinase (GSK)-3β signalling pathway in mediating the protective effects of tanshinone IIA (TSN) on diabetic cardiomyopathy.. Streptozocin (STZ) induced diabetic rats (n = 60) were randomized to receive TSN, TSN plus HOE140 (a kinin B2 receptor antagonist), or saline. Healthy Sprague-Dawley (SD) rats (n = 20) were used as control. Left ventricular function, myocardial apoptosis, myocardial ultrastructure, Akt, GSK-3β and NF-κB phosphorylation, the expression of TNF-α, IL-6 and myeloperoxidase (MPO) were examined. Cardiac function was well preserved as evidenced by increased left ventricular ejection fraction (LVEF) and ± dp/dt (maximum speed of contraction/relaxation), along with decreased myocardial apoptotic death after TSN administration. TSN pretreatment alleviated mitochondria ultrastructure changes. TSN also enhanced Akt and GSK-3β phosphorylation and inhibited NF-κB phosphorylation, resulting in decreased TNF-α, IL-6 and MPO activities. Moreover, pretreatment with HOE140 abolished the beneficial effects of TSN: a decrease in LVEF and ± dp/dt, an inhibition of cardiomyocyte apoptosis, a destruction of cardiomyocyte mitochondria cristae, a reduction of Akt and GSK-3β phosphorylation, an enhancement of NF-κB phosphorylation and an increase of TNF-α, IL-6 and MPO production.. These data indicated that TSN is cardioprotective in the context of diabetic cardiomyopathy through kinin B2 receptor-Akt-GSK-3β dependent pathway.

Topics: Abietanes; Animals; Apoptosis; Bradykinin; Cardiomyopathies; Cardiotonic Agents; Diabetes Mellitus, Experimental; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Interleukin-6; Mitochondria, Heart; Myocardial Contraction; Myocardium; NF-kappa B; Peroxidase; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Receptor, Bradykinin B2; Signal Transduction; Stroke Volume; Tumor Necrosis Factor-alpha; Ventricular Function, Left