title: The cardioprotective effect of sodium tanshinone IIA sulfonate and the optimizing of therapeutic time window in myocardial ischemia/reperfusion injury in rats.
abstract: OBJECTIVE
  The protective effect of sodium tanshinone IIA sulfonate (STS) pretreatment against experimental myocardial ischemia/reperfusion (I/R) has been demonstrated previously, however its therapeutic effects and mechanism of action still remain unclear. The objective of this study was to investigate the therapeutic time window and potential mechanism of STS action on myocardial I/R injury in a rat model of myocardial I/R.
  
  
  METHODS
  Rats received 30 min ischemia by complete ligation of the left ascending coronary artery, and then were reperfused for 24 h. STS (8 mg/kg) was administered intravenously 15 min before and at 0, 0.5, 1, 2, 4, 6 h after reperfusion. The infarct size and several consequences of myocardial I/R including myocardial zymogram, antioxidant status, cardiac function and microstructure disorder were evaluated 24 h after reperfusion. Furthermore, the effect of STS on heme oxygenase-1 (HO-1) protein expression and nuclear factor-κB (NF-κB) activation were also evaluated.
  
  
  RESULTS
  In the present study, the time point of optimal cardioprotective effect of STS was within 2 h after reperfusion, with declining effect at 4 h and no effect at 6 h after the onset of reperfusion. In addition, STS-mediated cytoprotection against oxidative stress and inflammatory responses was correlated with an increased HO-1 activity..
  
  
  CONCLUSIONS
  STS could ameliorate cardiac dysfunction and variation of myocardial zymogram, up-regulate antioxidant systems. Moreover, modulation of HO-1 was involved in STS induced cardioprotection..
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: weibozz101@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: huijicpu@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Ji
mesh_terms: D000818:Animals; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D016328:NF-kappa B / Q000096:biosynthesis; D010616:Phenanthrenes / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D010616:Phenanthrenes; D014409:Tumor Necrosis Factor-alpha; C024894:tanshinone II A sodium sulfonate; D051547:Heme Oxygenase-1
keywords: Inflammatory response; Myocardial ischemia reperfusion; Oxidative stress; Sodium tanshinone IIA sulphonate