英GSPE 心肌细胞 氧化损伤.pdfVIP

Pharmacological Research 47 2003 463–469 Grape seed proanthocyanidin extract attenuates oxidant injury in cardiomyocytes Zuo-Hui Shao a,b , Lance B. Becker a,b , Terry L. Vanden Hoek a,b , Paul T. Schumackerb , Chang-Qing Li a,b , Danhong Zhao a,b , Kim Wojcikb , Travis Anderson a,b , Yimin Qin b , Lucy Dey c,d , Chun-Su Yuanb,c,d,? a Department of Medicine, Section of Emergency Medicine, University of Chicago, 5841 S. Maryland Avenue, MC 5068, Chicago, IL 60637, USA b Emergency Resuscitation Center, University of Chicago, 5841 S. Maryland Avenue, MC 5068, Chicago, IL 60637, USA c Department of Anesthesia Critical Care, The University of Chicago, 5841 S. Maryland Avenue, MC 4028 Chicago, IL 60637, USA d Tang Center for Herbal Medicine Research, University of Chicago, 5841 S. Maryland Avenue, MC 4028, Chicago, IL 60637, USA Accepted 30 December 2002 Abstract This study sought to test whether grape seed proanthocyanidin extract GSPE attenuates exogenous and endogenous oxidant stress induced in chick cardiomyocytes and whether this cytoprotection is mediated by PKC activation, mito KATP channel opening, NO produc- tion, oxidant scavenging, or iron chelating effects. Cells were exposed to hydrogen peroxide H O exogenous oxidant stress, 0.5 mM or 2 2 antimycin A endogenous oxidant stress, 100 M for 2 h following pretreatment with GSPE at various concentrations for 2 h. Cells were also pretreated with GSPE or with inhibitors of PKC chelerytherine , mito KATP channel 5-hydroxydecanoate , nitric oxide synthase nitro-l-arginine methyl ester for 2 h. Oxidant stress was measured by 2 ,7 -dichloro?uorescin diacetate and cell viability was assessed using propidium iodide. Free radical scavenging and iron chelating ability was tested in vitro. GSPE dose-dependently attenuated oxidant formation and signi?cantly improved cell survival and contractile function. However, inhibitors of PKC, mito KATP channel or NO synthase failed to abolish the protective