Liu L-F, Qin Q, Qian Z-H, Shi M, Deng Q-C, Zhu W-P, Zhang H, Tao X-M, Liu Y
Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Soochow University, Suzhou, China.
Eur Rev Med Pharmacol Sci. 2014;18(23):3681-6.
To investigate the mechanism of melatonin (MT) protection of adult rate myocardial ischemia-reperfusion injury and its influence on rat's hemodynamic recovery.
48 rats were randomly divided into MT group (n=36) and the control group (n=12), MT group was divided into three sub-groups according to different dosages: Group I (n=12) was administered with 2.5 mg/kg MT; Group II (n=12) was administered with 5 mg/kg MT; Group III (n=12) was administered with 10 mg/kg MT. The electrocardiogram of four groups was observed with the left coronary artery blocked for 10min at first and then reperfused for 15min. Hemodynamic evolving was observed and changes in energy metabolism of rat myocardium were monitored. TUNEL and immunohistochemistry were applied to detect the cell apoptosis index, protein expression of Bcl-2 and Bax.
LVDP (left ventricular developed pressure) and ± dp/dt in MT group presented better recovery at various time points than the control group. Among them, Group III had the optimal recovery degree (p < 0.05). After MT administration, ATP content in myocardial cells in MT group was significantly higher than the control group. Compared with the control group, the concentration of mitochondrial MDA and Ca2+ in myocardial cells in MT group showed a downward trend. But its GSH concentration was significantly higher than the control group (p < 0.05). The improvement degree of ATP, MDA, GSH and Ca2+ concentration in Group II over-performed Group I (p < 0.05). MT-intervened myocardial apoptosis index (AI) and Bax positive expression index declined while Bcl-2 positive expression index increased (p < 0.01).
MT effectively inhibited myocardial apoptosis during the myocardial ischemia-reperfusion of rats, protected the structural integrity of mitochondria in myocardial cells, promoted ATP synthesis, and avoided heart damage in many ways. This protection mechanism was related with anti-oxidative damage. Meanwhile, MT could promote the hemodynamic recovery after myocardial ischemia-reperfusion in rats.
探讨褪黑素（MT）对成年大鼠心肌缺血再灌注损伤的保护机制及其对大鼠血流动力学恢复的影响。
48只大鼠随机分为MT组（n = 36）和对照组（n = 12），MT组根据不同剂量分为三个亚组：I组（n = 12）给予2.5mg/kg MT；II组（n = 12）给予5mg/kg MT；III组（n = 12）给予10mg/kg MT。首先结扎左冠状动脉10分钟，然后再灌注15分钟，观察四组的心电图。观察血流动力学变化，并监测大鼠心肌能量代谢的变化。采用TUNEL法和免疫组化法检测细胞凋亡指数、Bcl-2和Bax蛋白表达。
MT组左室舒张末压（LVDP）及±dp/dt在各时间点的恢复情况均优于对照组。其中，III组恢复程度最佳（p < 0.05）。给予MT后，MT组心肌细胞内ATP含量显著高于对照组。与对照组相比，MT组心肌细胞线粒体MDA和Ca2+浓度呈下降趋势。但其GSH浓度显著高于对照组（p < 0.05）。II组ATP、MDA、GSH和Ca2+浓度的改善程度优于I组（p < 0.05）。MT干预后心肌凋亡指数（AI）和Bax阳性表达指数下降，而Bcl-2阳性表达指数升高（p < 0.01）。
MT能有效抑制大鼠心肌缺血再灌注过程中的心肌细胞凋亡，保护心肌细胞线粒体结构完整性，促进ATP合成，从多方面避免心脏损伤。这种保护机制与抗氧化损伤有关。同时，MT可促进大鼠心肌缺血再灌注后血流动力学的恢复。
