title: Tanshinone IIA pretreatment protects myocardium against ischaemia/reperfusion injury through the phosphatidylinositol 3-kinase/Akt-dependent pathway in diabetic rats.
abstract: OBJECTIVE
  Diabetes Mellitus (DM) is widely acknowledged to increase the risk of cardiovascular death, which warrants the use of aggressive primary prevention strategies. The aim of the present study was to investigate the pretreatment effects of tanshinone IIA (TSN), a traditional Chinese medicine, on myocardial infarct size, apoptosis, inflammation and cardiac functional recovery in diabetic rats subjected to myocardial ischaemia/reperfusion (I/R).
  
  
  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-kappaB 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-kappaB 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-kappaB 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.
authors.affiliation: Department of Cardiovascular Medicine, Fourth Military Medical University, Xi'an, Shaanxi 710032., China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Wei
authors.forename: D
authors.initials: D
authors.lastname: Sun
authors.forename: F
authors.initials: F
authors.lastname: Cao
authors.forename: H
authors.initials: H
authors.lastname: Gao
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.forename: J
authors.initials: J
authors.lastname: Du
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Wang
mesh_terms: D045784:Abietanes; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology; D017202:Myocardial Ischemia / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D010616:Phenanthrenes / Q000494:pharmacology*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D000077191:Wortmannin
chemical_list: D045784:Abietanes; D000730:Androstadienes; D000925:Anticoagulants; D010616:Phenanthrenes; C021751:tanshinone; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin