Tanshinone IIA pretreatment protects myocardium against ischaemia/reperfusion injury through the phosphatidylinositol 3-kinase/Akt-dependent pathway in diabetic rats

Methods: Streptozocin (STZ) induced diabetic rats (n = 80) were randomized to receive TSN, TSN plus wortmannin [a phosphatidylinositol 3-kinase (PI3K) inhibitor] or saline. They were exposed to a 30-min ischaemia by ligation of the left coronary artery except for the sham group. Haemodynamics, infarct size and myocardial apoptosis were examined 3 h after reperfusion. The effects of TSN on Akt and NF-kappa B phosphorylation and the expression of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in cardiac tissues were examined. Results: Our results revealed that TSN administration significantly reduced myocardial infarct size (0.252 +/- 0.038 vs. 0.327 +/- 0.027, p < 0.05), improved left ventricular ejection fraction (LVEF) (0.774 +/- 0.058 vs. 0.716 +/- 0.054, p < 0.05), decreased myocardial apoptotic death (0.114 +/- 0.026 vs. 0.191 +/- 0.023, p < 0.05) compared with I/R group. Western blot analysis showed that TSN treatment enhanced Akt phosphorylation and inhibited NF-kappa B phosphorylation in cardiac tissues. Moreover, pretreatment with wortmannin abolished the beneficial effects of TSN: a reduction of infarct size, a decrease in LVEF, inhibition of myocardial apoptosis and Akt phosphorylation, enhancement of NF-kappa B phosphorylation and an increase of cytokine production including TNF-alpha and IL-6 after I/R injury in diabetic rats. Conclusions: This study indicates that TSN pretreatment reduces infarct size and improves cardiac dysfunction after I/R injury in diabetic rats. This was accompanied with decreased cardiac apoptosis and inflammation. The possible mechanism responsible for the effects of TSN is associated with the PI3K/Akt-dependent pathway.