Urantide对实验性心肌缺血及缺氧再给氧损伤的影响

Effects of urantide on myocardial ischemia and anoxia/reoxygenation injury

目的探讨urantide对心肌细胞急性缺血及缺氧再给氧损伤的保护作用。方法采用皮下注射(sc)异丙肾上腺素(Iso)诱导小鼠急性心肌缺血,测定小鼠心肌组织及血清中肌酸激酶(CK)、超氧化物歧化酶(SOD)的活性以及丙二醛(MDA)、一氧化氮(NO)的含量,计算心肌含水量(MWC)及心肌指数(MI)。建立乳鼠原代心肌细胞缺氧再复氧模型,观察细胞存活情况并检测urantide对细胞培养上清液中CK活性和MDA含量的影响。结果10、30μg/kgurantide可显著降低小鼠心肌组织及血清中CK活性,明显升高NO含量;3～30μg/kgurantide可呈浓度依赖性降低小鼠血清及心肌组织中MDA含量,升高SOD活性。同时,urantide10、30μg/kg剂量组可显著降低小鼠的MWC,显著抑制其MI的升高。在乳鼠原代心肌细胞缺氧再复氧模型中,10-6和10-7mol/L的urantide能明显增加细胞存活率,urantide在10-6～10-10mol/L浓度范围内能呈剂量依赖性抑制细胞培养上清液中CK活性和MDA含量的增高。结论实验表明urantide对心肌缺血损伤具有一定的保护作用,其作用机制可能与改善低灌流、清除氧自由基及抗脂质过氧化有关。

Objective To study the protective effect of urantide on myocardial ischemia injury in mouse and its mechanism. Methods The ischemia model was made by using subcutaneous injection of isoproterenol （Iso） in mouse, the change of ST segment of electrocardiograph （ECG） was observed, and the activity of superoxide dismutase （SOD） and creatine kinase （CK） ,the contents of malonaldehyde （MDA） and nitric oxide （NO） in serum were measured. We also calculate myocardium water content （MWC） and myocardium index number （MI）. An anoxia/reoxygenation （A/R） model of myocardial cells from neonatal Wistar rats was also established. Methyl thiazolyl tetrazolium （MTY） assay was used to measure the viability of myocardial cells exposed to A/R. CK activity and MDA content in the cell culture medium were assayed for the evaluation of myocardial cells injury. Results 10,30μg/kg significantly reduced the increases of NO content and CK activity in mouse serum and myocardiam, lowered MWC and MI. 3 - 30μg/kg urantide also raised the activity of SOD and the content of MDA by concentration dependent. On the anoxia/reoxygenation model of myocardial cells, 10-6-10^-7 mol/L urantide could evident- ly inhibit the increases of CK activity and MDA content by dose dependent. 10^-6- 10^-7 mol/L urantide could also increase the viability of myocardial cells injured by A/R. Conclusion Urantide has significant protective effect against myocardial ischemia or anoxia/reoxygenation injury via relaxing coronary artery, inhibiting lipid peroxidation and eliminating oxygen free radical.