title: Protective effect of picroside II on myocardial ischemia reperfusion injury in rats.
abstract: The aim of this study was to determine the effect of picroside II on myocardial ischemia reperfusion injury in rats and to explore its underlying mechanism. Isolated rat hearts underwent 30 minutes of global ischemia followed by 120 minutes of reperfusion. Different doses of picroside II (1 μM, 10 μM, and 100 μM) were given 20 minutes before ischemia. Phosphoinositide 3-kinase inhibitor (wortmannin) and nitric oxide synthase (NOS) inhibitor (L-N(G)-nitroarginine methyl ester) were given 10 minutes before picroside II treatment. The cardiac function, myocardial infarct size, apoptosis, myocardial nitric oxide content, the expressions of Bcl-2 and Bax, and the activation of the phosphoinositide 3-kinase/Akt/endothelial NOS pathway were evaluated. Treatment with 10 μM and 100 μM picroside II significantly improved postischemic myocardial function, reduced myocardial infarct size, inhibited apoptosis, increased myocardial NO content, upregulated Bcl-2, downregulated Bax, and increased the phosphorylation of Akt and endothelial NOS, but cardioprotection was not shown in the 1 μM picroside II treatment group and was abrogated by wortmannin and L-N(G)-nitroarginine methyl ester. Furthermore, cardioprotection in the 100 μM picroside II treatment group was superior to that in the 10 μM picroside II treatment group. In conclusion, the data reveals that picroside II has a significant protective effect on myocardial ischemia reperfusion injury in a dose-dependent manner, which was mediated by upregulating the phosphoinositide 3-kinase/Akt/endothelial NOS pathway to increase nitric oxide production and regulating the expressions of Bcl-2 and Bax to inhibit apoptosis.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Wenna
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Wenqi
authors.initials: W
authors.lastname: Shu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Dalin
authors.initials: D
authors.lastname: Jia
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002934:Cinnamates / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D057888:Iridoid Glucosides / Q000627:therapeutic use*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000032:analysis; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects; D000077191:Wortmannin; D051028:bcl-2-Associated X Protein / Q000032:analysis
chemical_list: D000730:Androstadienes; C494828:Bax protein, rat; D002934:Cinnamates; D057888:Iridoid Glucosides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D009569:Nitric Oxide; C416837:picroside II; D051057:Proto-Oncogene Proteins c-akt; D019331:NG-Nitroarginine Methyl Ester; D000077191:Wortmannin
keywords: apoptosis; endothelial nitric oxide synthase; ischemia reperfusion injury; nitric oxide; picroside II