Glimepiride treatment upon reperfusion limits infarct size via the phosphatidylinositol 3-kinase/Akt pathway in rabbit hearts.
Glimepiride treatment upon reperfusion limits infarct size via the phosphatidylinositol 3-kinase/Akt pathway in rabbit hearts.
复制标题
再灌注时格列美脲治疗通过兔心脏中的磷脂酰肌醇 3-激酶/Akt 途径限制梗死面积。
DOI：
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发表时间：
2009
影响因子：
3.5
通讯作者：
H. Nakaya
中科院分区：
文献类型：
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作者：
Hirofumi Nishida;Toshiaki Sato;M. Nomura;M. Miyazaki;H. Nakaya
这种被称为后处理的现象，即在再灌流开始时短暂的缺血/再灌流可以减少梗塞面积，被认为涉及磷脂酰肌醇3-激酶(PI3K)/Akt通路的激活。在再灌流开始时使用激活PI3K的药物治疗可能会提供类似的心脏保护。研究表明，磺脲类药物格列美脲能激活人内皮细胞中的PI3K。因此，我们在兔的心脏上测试了格列美脲是否能产生类似后处理的作用。采用Langendorff灌流的兔心，全脑缺血30min，再灌流120min，三苯基四氮唑染色测定心肌梗死面积。用Western blotting分析Akt的磷酸化。格列美脲(10微米)在再灌流前10分钟显著减少梗塞面积，从对照组的67.2+/-1.3%减少到35.8+/-4.5%(P<；0.01)。格列美脲的这种梗塞面积限制作用可被PI3K选择性抑制剂(5微米LY294002，65.4+/-3.4%)所消除。与对照组相比，格列美脲治疗组心脏中PI3K底物Akt的磷酸化显著增加(P<；0.05)。LY294002可抑制格列美脲诱导的Akt磷酸化。综上所述，我们的研究表明，格列美脲在再灌流时通过PI3K/Akt介导的途径减少兔心脏梗死范围。格列美脲的后处理模拟作用可能有益于糖尿病合并缺血性心脏病的治疗。
The phenomenon termed postconditioning, that is, brief episodes of ischemia/reperfusion at the onset of reperfusion reduce infarct size, is thought to involve the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Treatment with a drug activating PI3K at the onset of reperfusion may confer a similar cardioprotection. The sulfonylurea glimepiride has been shown to activate PI3K in human endothelial cells. We therefore tested in rabbit hearts whether glimepiride can produce postconditioning-mimetic actions. Langendorff-perfused rabbit hearts were subjected to 30 min of global ischemia and 120 min of reperfusion, and infarct size was determined by triphenyltetrazolium staining. Phosphorylation of Akt was analyzed by Western blotting. Glimepiride (10 microM) treatment for the first 10 min of reperfusion significantly reduced infarct size from 67.2 +/- 1.3% in controls to 35.8 +/- 4.5% (P < 0.01). This infarct size-limiting effect of glimepiride was abolished by a selective inhibitor of PI3K (5 microM LY294002, 65.4 +/- 3.4%). Phosphorylation of the PI3K substrate Akt was significantly increased in glimepiride-treated hearts when compared to controls (P < 0.05). Glimepiride-induced Akt phosphorylation was inhibited by LY294002. In conclusion, our study demonstrates that glimepiride treatment upon reperfusion reduces infarct size in rabbit hearts via a PI3K/Akt-mediated pathway. The postconditioning-mimetic action of glimepiride may be beneficial for the treatment of diabetic patients with ischemic heart disease.
影响因子：
24
作者：
Yang, XM;Proctor, JB;Cohen, MV
通讯作者：
Cohen, MV