【摘要】 目的:观察心肌缺血再灌注损伤过程中血清中一氧化氮的浓度,一氧化氮合酶及铜锌-超氧化物歧化酶的活性,分析葡萄糖酸锌对心肌的保护作用及其可能机制。方法:实验于2005-10/2006-05在锦州医学院药理学实验室进行,50只SD大鼠随机分为5组,即假手术组,缺血再灌注模型组,葡萄糖酸锌167,250,357mg/kg剂量组。采用左冠状动脉下穿线,拉紧丝线引起心肌缺血,放松丝线给予再灌注的方法建立心肌缺血再灌注损伤动物模型,假手术组,完成模型全部操作,只穿线不结扎。葡萄糖酸锌167,250,357mg/kg剂量组,分别以相应剂量葡萄糖酸锌(溶于蒸馏水中,2mL)灌胃,每次2mL,上下午各1次,两次灌胃给药间隔时间为2.5h。于末次灌胃1h后行冠状动脉左前降支结扎30min,再灌注60min。缺血再灌注模型组,给予等容量的生理盐水灌胃,其他处理同上。采用硝酸还原酶化学比色法测定血清中一氧化氮浓度及一氧化氮合酶活性,抽提法测定血清中铜锌超氧化物歧化酶活性。结果:50只大鼠进入结果分析。①模型组大鼠血清中一氧化氮浓度、血清中总一氧化氮合酶、诱导型一氧化氮合酶及铜锌超氧化物歧化酶的活性较假手术组升高,结构型一氧化氮合酶的活性降低(P<0.01～0.05)。②葡萄糖酸锌250,357mg/kg组大鼠血清一氧化氮浓度较模型组升高(P<0.05,0.01);葡萄糖酸锌167,250,357mg/kg组大鼠血清中总一氧化氮合酶的活性及血清中结构型一氧化氮合酶的活性较模型组升高(P<0.01,0.05),血清中诱导型一氧化氮合酶的活性降低(P<0.01,P<0.05);葡萄糖酸锌357mg/kg组大鼠血清中铜锌-超氧化物歧化酶的活性升高(P<0.01)。③血清中铜锌-超氧化物歧化酶活性与一氧化氮浓度呈正相关(r=0.92,P<0.01)。结论:葡萄糖酸锌对缺血再灌注心肌具有保护作用,作用途径可能为:①通过降低诱导型一氧化氮合酶的活性,增强结构型一氧化氮合酶的活性而提高一氧化氮水平。②参与构成铜锌-超氧化物歧化酶,清除自由基。更多还原

【Abstract】 AIM: This paper was to observe the concentration of nitrogen monoxidum (NO) and the activities of nitricoxide synthase (NOS) and CuZn-superoxide dismutase (SOD) in the blood serum to investigate the cardioprotective effect and possible mechanism of zinc gluconate (ZG) during myocardial ischemia reperfusion injury in anesthetized rats. METHODS: The experiment was performed in the Pharmacology Laboratory of Jinzhou Medical College from October 2005 to May 2006. Fifty SD rats were randomly divided into five groups: sham, model, ZG groups of 167, 250 and 357 mg/kg. Left coronary artery braid, silk suture tense and silk suture slacken were adopted to establish the model of myocardial ischemia reperfusion injury in anesthetized rats, while the sham group was given all the procedures except ligation. ZG groups were injected with corresponding concentrations of ZG intragastrically, 2 mL once and two times per day, with the interval of 2.5 hours. One hour after the last administration, the rats were ligated for 30 minutes and reperfused for 60 minutes in the left anterior descending branch of coronary artery. Whereas the rats of model group was injected with equal volume of saline intragastrically. Nitrate reductase chemical colorimetry was used to determine the concentration of NO and the activity of NOS total NOS (tNOS), constitutive NOS (cNOS) and inducing NOS (iNOS) in the blood serum. CuZn-SOD activity was detected by extract method. RESULTS: All the 50 rats were involved in the analysis of results.① Compared with the sham, the model group increased the concentration of NO, the activities of tNOS and iNOS as well as CuZn-SOD in the blood serum, but decreased the activity of cNOS (P < 0.01-0.05).② Compared with the model group, ZG of 250 mg/kg and 357 mg/kg increased the concentration of NO (P < 0.05, 0.01). The activity of tNOS and cNOS were increased whereas the activity of iNOS was decreased in three ZG groups (P < 0.05, 0.01). The activity of CuZn-SOD increased in 357 mg/kg ZG group (P < 0.01).③The CuZn-SOD activity was positively correlated with NO concentration (r =0.92, P < 0.01). CONCLUSION: ZG has protective effects on myocardial ischemia reperfusion injury. The effects may decrease the activity of iNOS and increase the activity of cNOS so as to elevate the concentration of NO; moreover, it can clean free radical by participating in CuZn-SOD composition.更多还原