Wu Nan, Li Wenna, Shu Wenqi, Jia Dalin
Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
Drug Des Devel Ther. 2014 May 14;8:545-54. doi: 10.2147/DDDT.S62355. eCollection 2014.
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.
本研究旨在确定胡黄连苷II对大鼠心肌缺血再灌注损伤的影响，并探讨其潜在机制。离体大鼠心脏先进行30分钟的全心缺血，然后再灌注120分钟。在缺血前20分钟给予不同剂量的胡黄连苷II（1 μM、10 μM和100 μM）。在给予胡黄连苷II治疗前10分钟给予磷酸肌醇3激酶抑制剂（渥曼青霉素）和一氧化氮合酶（NOS）抑制剂（L-N(G)-硝基精氨酸甲酯）。评估心脏功能、心肌梗死面积、细胞凋亡、心肌一氧化氮含量、Bcl-2和Bax的表达以及磷酸肌醇3激酶/Akt/内皮型NOS途径的激活情况。10 μM和100 μM胡黄连苷II治疗可显著改善缺血后心肌功能，减小心肌梗死面积，抑制细胞凋亡，增加心肌NO含量，上调Bcl-2，下调Bax，并增加Akt和内皮型NOS的磷酸化，但1 μM胡黄连苷II治疗组未显示出心脏保护作用，且渥曼青霉素和L-N(G)-硝基精氨酸甲酯可消除这种保护作用。此外，100 μM胡黄连苷II治疗组的心脏保护作用优于10 μM胡黄连苷II治疗组。总之，数据表明胡黄连苷II对心肌缺血再灌注损伤具有显著的剂量依赖性保护作用，其机制是通过上调磷酸肌醇3激酶/Akt/内皮型NOS途径以增加一氧化氮生成，并调节Bcl-2和Bax的表达以抑制细胞凋亡。
