目的:采用选择性κ阿片受体激动剂U50488H激活κ阿片受体,观察其对缺血再灌注大鼠心肌梗死面积以及血管紧张素Ⅱ、内皮素和NO的影响.方法:实验于2002-03/2003-05在解放军第四军医大学生理学教研室完成.选用健康雄性成年SD大鼠32只,随机分为4组(n=8):①对照组:未结扎冠状动脉左前降支.②缺血再灌注组:结扎冠状动脉左前降支,给予心肌缺血45 min,并再灌注15 min.③U50488H组:预先给予U50488H 1.5 mg/kg,15 min后造模,方法同缺血再灌注组.④NorBNI组:在给予U50488H 10 min前先给予选择性κ阿片受体阻断剂Nor-BNI 0.5 mg/kg,余同U50488H组.观察各组大鼠心肌超微结构、心肌梗死面积以及血浆肌酸磷酸激酶、乳酸脱氢酶、血管紧张素Ⅱ、内皮素和一氧化氮等因子的水平.结果:32只大鼠进入结果分析.①心肌梗死面积:U50488H组小于缺血再灌注组和Nor-BNI组[(0.039±0.01),(0.085±0.01),(0.077±0.02)cm^2,P<0.01],后两组差异不显著.②血浆中肌酸磷酸激酶和乳酸脱氢酶活性:缺血再灌注组大鼠高于对照组(P<0.01),U50488H组明显低于缺血再灌注组(P<0.01).③血管紧张素Ⅱ水平:缺血再灌注组大鼠高于对照组[(305±38),(134±26)ng/L,P<0.01],U50488H组明显低于缺血再灌注组[(197±23)ng/L,P<0.01].④内皮素:缺血再灌注组大鼠高于对照组[(366±32),(179±24)ng/L,P<0.01],U50488H组明显低于缺血再灌注组[(242±27)ng/L,P<0.01].⑤一氧化氮浓度:缺血再灌注组大鼠低于对照组[(21±6),(58±9)mol/L,P<0.01],U50488H组明显高于缺血再灌注组[(44±8)mol/L,P<0.01].结论:U50488H可通过激活心脏κ阿片受体发挥心脏保护作用,并可以减少心肌酶的漏出,下调血管紧张素Ⅱ、内皮素水平以及上调一氧化氮水平.
AIM: To observe the effects of selective κ-opioid receptor agonist U50488H on the infarction size, angiotensin Ⅱ (AT Ⅱ ), endothelin (ET) and nitric oxide (NO) in rats with myocardial ischemic reperfusion injury by activating the κ-opioid receptor agonist with U50488H. METHODS: The experiment was conducted in the Department of Physiology, Fourth Military Medical University of Chinese PLA between March 2002 and May 2003. Thirty-two healthy male adult rats were randomly divided into four groups (n=8): ①control group: the left anterior descending coronary artery (LADCA) of rats was not deligated.②Ischemic reperfusion group: rats were deligated of the LADCA, and received 15-minute reperfusion following myocardial isehemia (MI).③U50488H group: rats were given 1.5 mg/kg U50488H in advance, and modeling was conducted at 15 minutes later with the same method as the ischemic reperfusion group. ④Nor- BNI group: 10 minutes before the administration of U50488H, rats were administrated with 0.5 mg/kg selective κ-opioid receptor blocking pharmacon Nor-BNI, and the rests were the same as the U50488H group. The myocardial uhrastructure, infarction size and levels of plasma creatine phosphokinase, lactic dehydrogenase (LAD), AT Ⅱ , ET and NO were observed. RESULTS: A total of 32 rats were involved in the analysis of results. ① Infarction size: That of U50488H group was smaller than the ischemic reperfusion group and Nor-BNI group [(0.039 ±0.01), (0.085 ±0.01.), (0.077±0.02) cm^2,P 〈 0.01], while the differences between the latter two groups were not significant. ②The activities of creatine phosphokinase and LAD in plasma: Those in rats of the ischemic reperfusion group were higher than the control group (P 〈 0.01), and those in the U50488H group were significantly lower than the ischemic reperfusion group (P 〈 0.01). ③The level of AT Ⅱ : that in the ischemic reperfusion group was higher than the control group [(305±38), ?