ISSN 2996-8215
International Journal of Cardiology | Vol. 1, No. 7, July 2010 | pp. 49–56
DOI: 10.46882/2010/IJC/000016
Original Research Article
Cardioprotective Effects of Resveratrol in a Rat Model of Ischemia-Reperfusion Injury: Role of the SIRT1 Pathway
Li Wei¹, Zhang Min¹, Wang Wei²
¹State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, China
²Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China
Abstract:
Myocardial ischemia-reperfusion (I/R) injury leads to irreversible tissue damage, cardiac dysfunction, and cardiomyocyte apoptosis. Resveratrol, a natural polyphenolic compound, possesses antioxidant and anti-apoptotic properties, but its underlying molecular mechanisms remain incompletely understood. This study investigated the protective effects of resveratrol against myocardial I/R injury in rats and explored the involvement of the Silent Information Regulator 1 (SIRT1) signaling pathway. Adult male Sprague-Dawley rats were randomized into four groups (n = 12 per group): Sham, I/R control, Resveratrol + I/R, and Resveratrol + EX527 (a SIRT1 inhibitor) + I/R. Ischemia was induced by occluding the left anterior descending coronary artery for 30 minutes, followed by 120 minutes of reperfusion. Resveratrol (20 mg/kg/day) was administered orally for 14 days prior to I/R. Pretreatment with resveratrol significantly reduced myocardial infarct size compared to the I/R control group (28.4% ± 3.5% vs. 44.6% ± 4.2%, p < 0.01). Resveratrol administration also preserved left ventricular developed pressure (LVDP) and attenuated the rise in serum creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) levels (p < 0.05). Furthermore, resveratrol up-regulated SIRT1 expression and down-regulated cleaved caspase-3 expression, leading to a marked reduction in TUNEL-positive apoptotic cardiomyocytes. Crucially, co-administration of the SIRT1 inhibitor EX527 abolished the infarct-limiting and anti-apoptotic benefits of resveratrol (infarct size: 41.2% ± 3.9%, p > 0.05 vs. I/R control). These findings indicate that resveratrol exerts potent cardioprotective actions against ischemia-reperfusion injury in rats by suppressing cardiomyocyte apoptosis via activation of the SIRT1 pathway.
Keywords: Ischemia-reperfusion injury, Resveratrol, SIRT1, Cardiomyocytes, Apoptosis, Infarct size
Received: April 10, 2010; Revised: May 20, 2010; Accepted: June 08, 2010; Published: July 25, 2010
Citation: International Journal of Cardiology, 2010, Vol. 1, No. 7, pp. 49–56, DOI: 10.46882/2010/IJC/000016