Protective effects of methylene blue on ischemia/reperfusion-induced mitochondrial injury in isolated rat hearts / 中国病理生理杂志

ABSTRACT

AIM:To study the effects of methylene blue (MB) on myocardial ischemia/reperfusion (I/R)-induced mitochondrial injury in isolated rat hearts.METHODS:Spragure-Dawley (SD) rats were divided into 3 groups randomly (n=6): control group, I/R model group and MB treatment group (IR+MB group).The isolated rat hearts were prepared and set up to Langendorff perfusion.The rats in I/R+MB group received MB (2 mg/kg) by intraperitoneal injection 2 h before operation.The hearts in control group were perfused with K-H solution for 110 min consecutively.The hearts in I/R group and I/R+MB group were in equilibrium for 20 min, following by 45 min of global ischemia, and then reperfused for 60 min.The heart rate (HR), left ventricular developed pressure (LVDP), left ventricular pressure maximum change rate (±dp/dtmax) and left ventricular end-diastolic pressure (LVEDP) were recorded.The perfusate was collected to determine the activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH).The contents of reactive oxygen species (ROS), malondialdehyde (MDA) and adenosine triphosphate (ATP), and the activity of superoxide dismutase (SOD) in the myocardial tissues were all determined.Histopathological examination of left ventricle was performed.The mitochondria from the heart tissues was isolated and the mitochondrial swelling and mitochondrial membrane potential (MMP) were analyzed.RESULTS:Compared with control group, the hearts in I/R group showed poorer function, higher CK-MB and LDH levels in the perfusate, increased ROS and MDA contents, higher SOD activity and less ATP content in the heart tissues (P<0.05).Furthermore, the mitochondrial swelling level increased and MMP reduced in I/R group (P<0.05).Compared to I/R group, MB improved heart function and reduced the release of CK-MB and LDH (P<0.05).MB also decreased ROS and MDA contents, and increased the activity of SOD and the content of ATP (P<0.05).In addition, MB alleviated mitochondrial swelling and restored the reduced MMP (P<0.05).CONCLUSION: MB protects the isolated rat hearts from I/R-induced injury by attenuating the damage of mitochondria.