Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
J Pineal Res. 2011 Mar;50(2):171-82. doi: 10.1111/j.1600-079X.2010.00826.x. Epub 2010 Nov 15.
Obesity, a major risk factor for ischemic heart disease, is associated with increased oxidative stress and reduced antioxidant status. Melatonin, a potent free radical scavenger and antioxidant, has powerful cardioprotective effects in lean animals but its efficacy in obesity is unknown. We investigated the effects of chronic melatonin administration on the development of the metabolic syndrome as well as ischemia-reperfusion injury in a rat model of diet-induced obesity (DIO). Male Wistar rats received a control diet, a control diet with melatonin, a high-calorie diet, or a high-calorie diet with melatonin (DM). Melatonin (4 mg/kg/day) was administered in the drinking water. After 16 wk, biometric and blood metabolic parameters were measured. Hearts were perfused ex vivo for the evaluation of myocardial function, infarct size (IFS) and biochemical changes [activation of PKB/Akt, ERK, p38 MAPK, AMPK, and glucose transporter (GLUT)-4 expression). The high-calorie diet caused increases in body weight (BW), visceral adiposity, serum insulin and triglycerides (TRIG), with no change in glucose levels. Melatonin treatment reduced the BW gain, visceral adiposity, blood TRIG, serum insulin, homeostatic model assessment index and thiobarbituric acid reactive substances in the DIO group. Melatonin reduced IFS in DIO and control groups and increased percentage recovery of functional performance of DIO hearts. During reperfusion, hearts from melatonin-treated rats had increased activation of PKB/Akt, ERK42/44 and reduced p38 MAPK activation. Chronic melatonin treatment prevented the metabolic abnormalities induced by DIO and protected the heart against ischemia-reperfusion injury. These beneficial effects were associated with activation of the reperfusion injury salvage kinases pathway.
肥胖是缺血性心脏病的一个主要危险因素，与氧化应激增加和抗氧化状态降低有关。褪黑素是一种有效的自由基清除剂和抗氧化剂，在瘦动物中具有强大的心脏保护作用，但在肥胖中的疗效尚不清楚。我们研究了慢性褪黑素给药对饮食诱导肥胖（DIO）大鼠模型中代谢综合征的发展以及缺血再灌注损伤的影响。雄性 Wistar 大鼠给予对照饮食、对照饮食加褪黑素、高热量饮食或高热量饮食加褪黑素（DM）。褪黑素（4mg/kg/天）在饮用水中给药。16 周后，测量生物计量和血液代谢参数。心脏在体外灌流以评估心肌功能、梗死面积（IFS）和生化变化[蛋白激酶 B/akt、细胞外信号调节激酶（ERK）、p38 丝裂原活化蛋白激酶（p38 MAPK）、腺苷酸活化蛋白激酶（AMPK）和葡萄糖转运体（GLUT）-4 表达的激活]。高热量饮食导致体重（BW）、内脏脂肪、血清胰岛素和甘油三酯（TRIG）增加，而血糖水平没有变化。褪黑素治疗降低了 DIO 组的 BW 增加、内脏脂肪、血液 TRIG、血清胰岛素、稳态模型评估指数和丙二醛反应物质。褪黑素降低了 DIO 和对照组的 IFS，并增加了 DIO 心脏功能恢复的百分比。在再灌注期间，褪黑素处理的大鼠心脏中 PKB/akt、ERK42/44 的激活增加，p38 MAPK 的激活减少。慢性褪黑素治疗可预防 DIO 引起的代谢异常，并保护心脏免受缺血再灌注损伤。这些有益作用与再灌注损伤挽救激酶途径的激活有关。
