Abstract:Objective: To detect the protective effects of paeonol on myocardial ischemia reperfusion (IR) in rats and explore the underlying mechanism. Methods: Sprague Dawley (SD) rats were used to establish myocardial ischemia-reperfusion injury model. Western blot was used to determine the expression level of sirtuin1 (SIRT1). Reactive oxygen species (ROS) of rats' myocardium tissue was analyzed by DCFDA. Oxidative stress markers malondialdehyde (MDA) and superoxide dismutase (SOD) and myocardial injury markers lactate dehydrogenase (LDH) and creatine kinase (CK) were evaluated by ELISA. Echocardiography was used for determining myocardial functions and left ventricular remodeling. Results: ROS generation was significantly decreased by paeonol pre-treatment. Besides, after paeonol treatment, MDA, LDH and CK were notably inhibited and SOD was elevated. Myocardial functions and left ventricular remodeling were improved by paeonol. Furthermore, paeonol significantly promoted SIRT1 and the effects were reversed by knocking down SIRT1. Conclusion: Paeonol alleviates oxidative stress and myocardial injury led by ischemia reperfusion, and thus improves myocardial functions and ventricular remodeling by promoting SIRT1.
[1] Spath NB, Mills NL, Cruden NL. Novel cardioprotective and regenerative therapies in acute myocardial infarction: a review of recent and ongoing clinical trials[J].Future Cardiol,2016,12(6):655~672. [2] Heusch G, Gersh BJ. The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: a continual challenge[J].Eur Heart ,2017,38(11):774~784. [3] Jin X, Wang J, Xia ZM, et al. Anti-inflammatory and anti-oxidative activities of paeonol and its metabolites through blocking MAPK/ERK/p38 signaling pathway[J].Inflammation,2016,39(1):434~446. [4] Nizamutdinova IT, Jin YC, Kim JS, et al. Paeonol and paeoniflorin, the main active principles of paeonia albiflora, protect the heart from myocardial ischemia/reperfusion injury in rats[J].Planta Med,2008,74(1):14~18. [5] Lee FY, Shao PL, Wallace CG, et al. Combined therapy with SS31 and mitochondria mitigates myocardial ischemia-reperfusion injury in rats[J].Int Mol Sci,2018,19(9): E2782. [6] Zhang Y, Wang XL, Zhao J, et al.Adiponectin inhibits oxidative/nitrative stress during myocardial ischemia and reperfusion via PKA signaling[J].Am Physiol Endocrinol Metab,2013,305(12):E1436~1443. [7] Choy KW, Lau YS, Murugan D, et al.Chronic treatment with paeonol improves endothelial function in mice through inhibition of endoplasmic reticulum stress-mediated oxidative stress[J].PLoS One,2017,12(5):e0178365. [8] Ding Y, Li Q, Xu Y, et al.Attenuating oxidative stress by paeonol protected against acetaminophen-induced hepatotoxicity in mice[J].PLoS One,2016,11(5):e0154375. [9] Shah SA, Khan M, Jo MH, et al.Melatonin stimulates the SIRT1/Nrf2 signaling pathway counteracting lipopolysaccharide (LPS)-induced oxidative stress to rescue postnatal rat brain[J].CNS Neurosci Ther,2017,23(1):33~44. [10] Hori YS, Kuno A, Hosoda R, et al.Regulation of FOXOs and p53 by SIRT1 modulators under oxidative stress[J].PLoS One,2013,8(9):e73875. [11] Wan X, Wen JJ, Koo SJ, et al.SIRT1-PGC1α-NFκB pathway of oxidative and inflammatory stress during trypanosoma cruzi Infection: benefits of SIRT1-targeted therapy in improving heart function in chagas disease[J].PLoS Pathog,2016,12(10):e1005954. [12] Yang B, Xu B, Zhao H, et al.Dioscin protects against coronary heart disease by reducing oxidative stress and inflammation via Sirt1/Nrf2 and p38 MAPK pathways[J].Mol Med Rep,2018,18(1):973~980.