Ginsenoside Rb1 preconditioning attenuates myocardial ischemia/reperfusion injury in diabetic rats

Abstract

OBJECTIVE: Diabetes mellitus is associated with decreased nitric oxide (NO) bioavailability in the myocardium. Ginsenoside Rb1, the effective component of the Chinese medicine Radix Gngseng, has been showed to confer cardioprotection against ischemia reperfusion injury [1]. The aim of this study was to investigate whether Ginsenoside Rb1 exerts cardioprotective effects during myocardial ischemia-reperfusion in diabetic rats and whether this effect is related to increase the production of NO via enhancing endothelial NO synthase (eNOS) expression in the myocardium. METHODS: Streptozotocin (65mg/kg) –induced diabetic SD rats were randomly divided into 5 groups: sham-operated (sham), ischemia/reperfusion (I/R), I/R treated, respectively, with ginsenoside Rb1 (40 mg/kg) (I/R plus Rb1) or N (G)-nitro-L- arginine methyl ester (L-NAME, 10mg/kg) (an eNOS inhibitor) (I/R plus L-NAME) or their combination (I/R plus RB1 and L-NAME). The myocardial I/R injury was induced by occluding the left main coronary artery for 30 min followed by 120 min reperfusion. L-NAME (10 mg•kg-1) or Rb1 (40 mg•kg-1) was respectively administered before 25 min or 10 min before inducing ischemia. Infarct size or tissue histological changes was respectively determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining and HE staining. Plasma creatine kinase (CK), lactate dehydrogenase (LDH) and myocardium malondialdehyde (MDA) level, superoxide dismutase (SOD) activity and concentration of NO at reperfusion 120 min were assayed by enzyme-liked immunosorbent assay. Expression of eNOS was detected by immumohistochemistry. RESULTS: Ginsenoside Rb1 preconditioning reduced myocardial infarct size when compared with I/R group (36.90±2.34% versus 51.67±4.34%, P[start_en]003C;0.01). This was accompanied with increased eNOS expression and NO concentration and reduced plasma CK and LDH in the ginsenoside Rb1 preconditioning group compared with control (all P < 0.05). Also, the myocardial oxidative stress and tissue histological damage was attenuated by ginsenoside Rb1 (P[start_en]003C;0.05). L-NAME abolished the protective effects of Rb1. CONCLUSION: It is concluded that ginsenoside Rb1 protects against myocardium ischemia/reperfusion injury in diabetic rat by enhancing the expression of eNOS and increasing the content of NO as well as inhibiting oxidative stress.