к阿片受体选择性激动剂U50488H对心肌梗死大鼠血管紧张素Ⅱ、内皮素和一氧化氮的影响  

Effects of selective kappa-opioid receptor agonist U50488H on angiotensin Ⅱ, endothelin and nitric oxide in rats with myocardial infarction

作　　者：张鹏[1] 朱运龙[1] 王跃民[1] 李明哲[1] 毕辉[1] 裴建明[1] 

机构地区：[1]解放军第四军医大学基础部生理学教研室,陕西省西安市710033

出　　处：《中国临床康复》2006年第22期77-79,共3页Chinese Journal of Clinical Rehabilitation

基　　金：国家自然科学基金资助项目(30370580);全军医药卫生科研基金军队"十五"计划课题(01MB129)~~

摘　　要：目的:采用选择性к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45min,并再灌注15min。③U50488H组:预先给予U50488H1.5mg/kg,15min后造模,方法同缺血再灌注组。④Nor-BNI组:在给予U50488H10min前先给予选择性к阿片受体阻断剂Nor-BNI0.5mg/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)cm2,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к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）, �

关 键 词：受体 阿片样 κ/激动剂 受体 阿片样 κ/拮抗剂和抑制剂 心肌梗塞 血管紧张素Ⅱ 内皮素 一氧化氮 

分 类 号：R542.2[医药卫生—心血管疾病]