Background: Our recent studiesdemonstrate that burn trauma induces leaky sarcoplasmic reticulum (SR) in heart due to excessively activeryanodine receptor (RyR) function.SR Ca2+leak causes partial depletion of SR Ca2+ content and disturbances of intracellular Ca2+homeostasis,resulting in the pathogenesis of burn-generated cardiac dysfunction.The present study investigated the role of polydatin,a resveratrol glucoside in preventing SR leak and the therapeutic effect against burn-generated cardiac dysfunction.Results: We found that polydatin treatment improved cardiac function impaired by burn injury of 30% of total body surface area.Parallel to the alteration of cardiac function,polydatin significantly increased the defective systolicCa2+ transient and contractility in burn-traumatized cardiomyocytes.Burn injury increased the occurrence of Ca2+ sparks.The enhancement of Ca2+ spark-mediated SR leak caused partial depletion of SR Ca2+ content in burn-traumatized cardiomyocytes.Furthermore,we found that the content of free thiols(the number of reduced cysteines) in RyR2 in cardiomyocytes determined by the monobromobimane (mBB) fluorescence of RyR2 was decreased markedly in burn-traumatized hearts.Polydatin treatment decreased intracellular reactive oxygen species (ROS) levels and restored the amount of free thiols in RyR2 in burns.Concomitantly,polydatin corrected Ca2+ spark-mediated SR leak and restored SR Ca2+load.The systolic Ca2+ transient and cellular contractility were significantly increased by polydatin treatment.Conclusion: The present findings provide first evidence demonstrating that polydatin prevented enhanced Ca2+ spark-mediated SR leak through reducing oxidative stress in RyR2 in burn-traumatized heart,leading to protection of cardiac function against burn injury.