【摘要】 目的:观察克罗卡林和硝酸甘油两药单用及合用抗大鼠心肌缺血的药理性预适应早期心脏保护作用。方法:实验于2005-10/2006-05在辽宁医学院药理学实验室进行。①实验分组和方法:取60只雄性SD大鼠随机分为6组,每组10只:假手术组:完成模型全部操作,只穿线不结扎。缺血再灌注组: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,缺血30min,再灌注60min。缺血预适应组:缺血前行缺血5min再灌注5min,共3个循环,余同缺血再灌注组。硝酸甘油组:100μg/kg尾静脉缓慢静脉滴注1h,再行缺血再灌注。克罗卡林组:100μg/kg尾静脉缓慢静注,30min后行缺血再灌注。硝酸甘油+克罗卡林组:缺血前1h静滴硝酸甘油100μg/kg,30min时静注克罗卡林,再行缺血再灌注。②实验评估:各组大鼠在再灌注60min后,经颈动脉取血采用比色法测定肌酸激酶;于实验结束后立即取左室游离心肌组织0.5g,采用羟胺法测定超氧化物歧化酶活性,硫代巴比妥钠比色法测定丙二醛含量,硝酸还原酶法测定一氧化氮含量,用虫荧光素酶法测定ATP含量。结果:60只大鼠进入结果分析。①血清中肌酸激酶活力:缺血预适应组、硝酸甘油组、克罗卡林组和硝酸甘油+克罗卡林组均低于缺血再灌注组(P<0.05),硝酸甘油+克罗卡林组下降更显著(P<0.01)。②心肌组织超氧化物酶活力:缺血预适应组、硝酸甘油组、克罗卡林组和硝酸甘油+克罗卡林组均高于缺血再灌注组(P<0.05或P<0.01),硝酸甘油+克罗卡林组高于硝酸甘油组、克罗卡林组(P<0.05)。③心肌组织内丙二醛含量:缺血预适应组、硝酸甘油组、克罗卡林组和硝酸甘油+克罗卡林组均低于缺血再灌注组(P<0.05或P<0.01)。④心肌组织内一氧化氮含量:缺血预适应组、硝酸甘油组、克罗卡林组和硝酸甘油+克罗卡林组均高于缺血再灌注组(P<0.05或P<0.0l),硝酸甘油+克罗卡林组高于硝酸甘油组、克罗卡林组(P<0.05)。⑤心肌组织ATP含量:缺血预适应组、硝酸甘油组、克罗卡林组和硝酸甘油+克罗卡林组均高于缺血再灌注组(P<0.05或P<0.01),硝酸甘油+克罗卡林组高于硝酸甘油组、克罗卡林组(P<0.05)。结论:硝酸甘油、色满卡林具有明显的抗大鼠心肌缺血的药理性预适应早期心脏保护作用,合用优于单用。更多还原

【Abstract】 AIM: To study the early cardioprotective effects of pharmacological preconditioning of cromakalim (CR) and nitroglycerin (NG) used alone and in combination on myocardial ischemia in rats. METHODS: The experiment was performed in the Pharmacological Laboratory of Liaoning Medical College from October 2005 to May 2006. ①Sixty male SD rats were selected and randomly divided into five groups (n =10): Sham operation group, in which the model was performed with all the steps only not to draw the suture; ischemia/reperfusion group (I/R), in which the models of myocardial I/R injury in anesthetized rats were established by drawing and releasing the suture advanced around the left coronary artery in rats with myocardial ischemia for 30 minutes and reperfusion for 60 minutes; ischemia preconditioning group (IPC), in which three cycles of ischemia for 5 minutes and then reperfusion for 5 minutes were performed; NG group, in which 100 μg/kg NG was intravenously injected into rats for 1 hour before myocardial ischemia and reperfusion; CR group: 100 μg/kg cromakalim was injected into the caudal vein of rats for 30 minutes before myocardial ischemia and I/R; NG+CR group: The time and method of injection were all the same to the nitroglycerin and cromakalim group. ②After reperfusion for 60 minutes, activities of creatine kinase (CK) in the blood serum gained from carotid artery were detected with chromatometry; 0.5 g myocardium of the left ventricle was harvested at the end of the experiment to detect the activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) were detected with hydroxylamine method and thiobarbituric acid calorimetric method, and the content of nitrogen monoxidum (NO) and ATP were detected with nitrate reduction and luciferase method. RESULTS: All the 60 rats were involved in the result analysis. ①Activity of serum CK in IPC, NG, CR and NG+CR groups was all decreased compared with that in I/R group (P < 0.05), especially NG+CR group (P < 0.01). ②Activity of SOD in myocardium of IPC, NG, CR and NG+CR groups was higher than that in I/R group (P < 0.05 or 0.0l), and NG+CR group was higher than NG and CR groups (P < 0.05). ③Contents of MDA in myocardium of IPC, NG, CR and NG+CR groups were all lower than that in I/R group (P < 0.05 or 0.0l). ④Contents of NO in IPC, NG, CR and NG+CR groups were higher than that in I/R group (P < 0.05 or 0.0l), and NG+CR group was higher than NG and CR groups (P < 0.05). ⑤Contents of ATP in IPC, NG, CR and NG+CR groups were higher than that that in I/R group (P < 0.05 or 0.0l), and NG+CR group was higher than NG and CR groups (P < 0.05). CONCLUSION: Pharmacological preconditioning of CR and NG has the distinct early cardioprotective effects on myocardial ischemia in rats; moreover, the combination use is superior to that of them alone.更多还原