Protective effect of ginsenoside Rb1 against myocardial ischemia/reperfusion injury in streptozotocin-induced diabetic rats

被引:82
作者
Wu, Yang [1 ]
Xia, Zhong-yuan [1 ]
Dou, Juan [2 ]
Zhang, Li [1 ]
Xu, Jin-jin [1 ]
Zhao, Bo [1 ]
Lei, Shaoqing [1 ]
Liu, Hui-min [1 ]
机构
[1] Wuhan Univ, Renmin Hosp, Dept Anesthesiol, Wuhan 430060, Hubei, Peoples R China
[2] Wuhan Univ, Renmin Hosp, Dept Cardiovasc Surg, Wuhan 430060, Hubei, Peoples R China
基金
中国国家自然科学基金;
关键词
Ginsenoside Rb1; Ginseng; Ischemia/reperfusion injury; Diabetes; Apoptosis; Akt; ISCHEMIA-REPERFUSION INJURY; NITRIC-OXIDE SYNTHASE; ENDOTHELIAL-CELLS; ESTROGEN-RECEPTOR; SIGNALING PATHWAY; AKT; ACTIVATION; HEART; PHOSPHORYLATION; KINASE;
D O I
10.1007/s11033-010-0558-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The objective of the current study is to investigate whether ginsenoside Rb1, a major pharmacological extract of ginseng that could attenuate myocardial ischemia reperfusion (MI/R) injury in non-diabetic myocardium, can attenuate MI/R injury in diabetes that are more vulnerable to ischemic insult. Rats were divided into seven groups: (i) diabetic sham, (ii) diabetic, (iii) normal, (iv) diabetic + ginsenoside Rb1, (v) diabetic + wortmannin, (vi) diabetic + wortmannin + ginsenoside Rb1, (vii) diabetic sham + wortmannin. Ginsenoside Rb1 and/or wortmannin were administered prior to inducing MI/R (30 min of coronary artery occlusion followed by 120 min reperfusion). At the end of the experiment, postischemic myocardial infarct size was significantly higher in the diabetic untreated group as compared to normal (P < 0.05), accompanied with increased myocardial apoptosis, elevated plasma CK-MB and LDH release and reduced blood pressure. Ginsenoside Rb1 reduced infarct size, cardiomyocyte apoptosis and caspase-3 activity compared to the diabetic group. The cardioprotective effects of ginsenoside Rb1 were cancelled by wortmannin. Ginsenoside Rb1 significantly upregulated phosphorylated Akt expression, which was attenuated by wortmannin. Ginsenoside Rb1 exerts cardioprotective effects against MI/R injury in diabetic rats, which is partly through activation of phosphatidylinositol 3-kinase (PI3 K)/Akt pathway. Thus this study shows a novel pharmacological preconditioning with ginsenoside Rb1 in the diabetic myocardium.
引用
收藏
页码:4327 / 4335
页数:9
相关论文
共 36 条
[1]   Attenuation of myocardial ischemia/reperfusion injury in mice with myocyte-specific overexpression of endothelial nitric oxide synthase [J].
Brunner, F ;
Maier, R ;
Andrew, P ;
Wölkart, G ;
Zechner, R ;
Mayer, B .
CARDIOVASCULAR RESEARCH, 2003, 57 (01) :55-62
[2]   Serine/threonine protein kinases and apoptosis [J].
Cross, TG ;
Scheel-Toellner, D ;
Henriquez, NV ;
Deacon, E ;
Salmon, M ;
Lord, JM .
EXPERIMENTAL CELL RESEARCH, 2000, 256 (01) :34-41
[3]   Diabetes and mortality following acute coronary syndromes [J].
Donahoe, Sean M. ;
Stewart, Garrick C. ;
McCabe, Carolyn H. ;
Mohanavelu, Satishkumar ;
Murphy, Sabina A. ;
Cannon, Christopher P. ;
Antman, Elliott M. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2007, 298 (07) :765-775
[4]   Nitric oxide mediates the antiapoptotic effect of insulin in myocardial ischemia-reperfusion -: The roles of PI3-kinase, akt, and endothelial nitric oxide synthase phosphorylation [J].
Gao, F ;
Gao, E ;
Yue, TL ;
Ohlstein, EH ;
Lopez, BL ;
Christopher, TA ;
Ma, XL .
CIRCULATION, 2002, 105 (12) :1497-1502
[5]   Diabetes abolishes morphine-induced cardioprotection via multiple pathways upstream of glycogen synthase kinase-3β [J].
Gross, Eric R. ;
Hsu, Anna K. ;
Gross, Garrett J. .
DIABETES, 2007, 56 (01) :127-136
[6]   Survival kinases in ischemic preconditioning and postconditioning [J].
Hausenloy, Derek J. ;
Yellon, Derek M. .
CARDIOVASCULAR RESEARCH, 2006, 70 (02) :240-253
[7]   New directions for protecting the heart against ischaemia-reperfusion injury: targeting the Reperfusion Injury Salvage Kinase (RISK)-pathway [J].
Hausenloy, DJ ;
Yellon, DM .
CARDIOVASCULAR RESEARCH, 2004, 61 (03) :448-460
[8]   Estrogen induces the Akt-dependent activation of endothelial nitric-oxide synthase in vascular endothelial cells [J].
Hisamoto, K ;
Ohmichi, M ;
Kurachi, H ;
Hayakawa, J ;
Kanda, Y ;
Nishio, Y ;
Adachi, K ;
Tasaka, K ;
Miyoshi, E ;
Fujiwara, N ;
Taniguchi, N ;
Murata, Y .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (05) :3459-3467
[9]   Angiotensin II Type 1 Receptor-Mediated Upregulation of Calcineurin Activity Underlies Impairment of Cardioprotective Signaling in Diabetic Hearts [J].
Hotta, Hiroyuki ;
Miura, Tetsuji ;
Miki, Takayuki ;
Togashi, Nobuhiko ;
Maeda, Takuto ;
Kim, Seok Jai ;
Tanno, Masaya ;
Yano, Toshiyuki ;
Kuno, Atsushi ;
Itoh, Takahito ;
Satoh, Takahiro ;
Terashima, Yoshiaki ;
Ishikawa, Satoko ;
Shimamoto, Kazuaki .
CIRCULATION RESEARCH, 2010, 106 (01) :129-U260
[10]   Ginsenoside Rb1 protects against 6-hydroxydopamine-induced oxidative stress by increasing heme oxygenase-1 expression through an estrogen receptor-related PI3K/Akt/Nrf2-dependent pathway in human dopaminergic cells [J].
Hwang, Yong Pil ;
Jeong, Hye Gwang .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 2010, 242 (01) :18-28