In vivo protective effects of urocortin on ischemia-reperfusion injury in rat heart via free radical mechanisms
In vivo protective effects of urocortin on ischemia-reperfusion injury in rat heart via free radical mechanisms
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DOI：
10.1139/y05-033
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发表时间：
2005-06-01
影响因子：
2.1
通讯作者：
Li, SN
中科院分区：
文献类型：
--
作者：
Liu, CN;Yang, C;Li, SN
本研究旨在探讨尿皮质素（UCN）对大鼠脑缺血再灌注损伤氧化应激的影响及其作用机制。将36只SD大鼠随机分为6组：假手术组、对照组（生理盐水）、UCN 1、UCN 2、UCN 3组和维拉帕米组。除假手术组外，其余各组大鼠冠状动脉左前降支结扎30 min，再灌注60 min。就在阻塞前，给予生理盐水溶液、UCN（5、10和20 μ g/kg体重）或维拉帕米（1 mg/kg体重）。使用ECG持续监测心率、搏动节律和S-T段。给药结束后取血测定超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-PX）和一氧化氮（NO）的活性，评价UCN对氧化应激的影响。最后测量梗死面积。与对照组相比，UCN组的心律失常发生率显著降低，梗死面积显著减小（p < 0.01）。维拉帕米也显著降低心律失常发生率和梗死面积。UCN组和VER组MDA活性明显降低，SOD、GSH-PX和NO活性明显升高（p < 0.01）。MDA、SOD和NO活性与UCN剂量密切相关。提示UCN可能通过抑制自由基活性对大鼠心肌缺血再灌注损伤起抗氧化作用。
The aim of this study was to investigate the effects of urocortin (UCN) on oxidative stress and the mechanisms of urocortin on ischemia-reperfusion injury in vivo in the rat model. Thirty-six Sprague-Dawley rats were divided into 6 groups, including sham, control (normal saline solution), UCN1, UCN2, UCN3, and verapamil groups. The left anterior descending coronary artery of all rats except those in the sham group was treated with a 30-min occlusion followed by a 60-min reperfusion. Just before the occlusion, normal saline solution, UCN (5, 10, and 20 mu g/kg body mass), or verapamil (I mg/kg body mass) was administered. Heart rates, beating rhythm, and S-T segments were constantly monitored using an ECG. At the completion of the drug adminstration, blood samples were taken to measure the activity of superoxide dismutase (SOD), malonaldehyde (MDA), glutathione peroxidase (GSH-PX), and nitric oxide (NO) to evaluate the effects of UCN on oxidative stress. Finally, the size of infarction was measured. Arrhythmia rates were significantly lower, and the infarction size was significantly smaller (p < 0.01), in the UCN groups vs. the control group. Verapamil also significantly reduced arrhythmia rates and infarction size. The MDA activities were remarkably diminished, whereas the SOD, GSH-PX, and NO activities were significantly higher in the UCN and VER groups (p < 0.01). MDA, SOD, and NO activities were strongly correlated with UCN doses. These results suggest that UCN may play a protective role in ischemia-reperfusion injury in rat hearts against the oxidative stress by inhibiting free radicals' activities.