Du Ying, Ko Kam Ming
Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Life Sci. 2005 Oct 14;77(22):2770-82. doi: 10.1016/j.lfs.2005.03.027.
Effects of emodin (EMD) treatment on mitochondrial ATP generation capacity and antioxidant components as well as susceptibility to ischemia-reperfusion (I-R) injury were examined in male and female rat hearts. Isolated-perfused hearts prepared from female rats were less susceptible to I-R injury than those of male rats. I-R caused significant decreases in ATP generation capacity and reduced glutathione (GSH) and alpha-tocopherol (alpha-TOC) levels as well as glutathione reductase, Se-glutathione peroxidase and Mn-superoxide dismutase (SOD) activities. The lower susceptibility of female hearts to myocardial I-R injury was associated with higher levels of GSH and alpha-TOC as well as activity of SOD than those of male hearts. EMD treatment at 3 daily doses (0.6 or 1.2 mmol/kg) could enhance myocardial mitochondrial ATP generation capacity and antioxidant components in both male and female rat hearts, but it only significantly protected against I-R injury in female hearts. Treatment with a single dose of EMD invariably enhanced mitochondrial antioxidant components and protected against I-R injury in both male and female hearts. The gender-dependent effect of EMD treatment at multiple doses may be related to the differential antioxidant response in the myocardium and/or induction of drug metabolizing enzymes in the liver.
在雄性和雌性大鼠心脏中，研究了大黄素（EMD）治疗对线粒体ATP生成能力、抗氧化成分以及缺血再灌注（I-R）损伤易感性的影响。与雄性大鼠相比，由雌性大鼠制备的离体灌注心脏对I-R损伤的敏感性较低。I-R导致ATP生成能力、还原型谷胱甘肽（GSH）和α-生育酚（α-TOC）水平以及谷胱甘肽还原酶、硒-谷胱甘肽过氧化物酶和锰超氧化物歧化酶（SOD）活性显著降低。雌性心脏对心肌I-R损伤的较低易感性与比雄性心脏更高水平的GSH、α-TOC以及SOD活性有关。每日3次剂量（0.6或1.2 mmol/kg）的EMD治疗可增强雄性和雌性大鼠心脏的心肌线粒体ATP生成能力和抗氧化成分，但仅对雌性心脏的I-R损伤有显著保护作用。单次剂量的EMD治疗总是能增强线粒体抗氧化成分，并对雄性和雌性心脏的I-R损伤起到保护作用。多次剂量的EMD治疗的性别依赖性效应可能与心肌中不同的抗氧化反应和/或肝脏中药物代谢酶的诱导有关。
