吗啡预处理对慢性心力衰竭大鼠心肌缺血再灌注损伤及心肌磷酸化细胞外信号调节激酶1／2表达的影响  

Effects of morphine preconditioning on myocardial ischemia-reperfusion injury and phosphorylated extra- cellular signal-regulated kinase 112 expression in rats with chronic heart failure

作　　者：吴运香[1] 张野[1] 姜凡[2] 翁立军[1] 胡宪文[1] 李云[1] 范礼斌 

机构地区：[1]安徽医科大学第二附属医院麻醉科,合肥市230601 [2]安徽医科大学第二附属医院超声诊断科,合肥市230601 [3]本大学生命科学院生物学教研室

出　　处：《中华麻醉学杂志》2011年第7期854-857,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（30672032）

摘　　要：目的探讨吗啡预处理对慢性心力衰竭大鼠心肌缺血再灌注损伤及心肌磷酸化细胞外信号调节激酶1／2（p-ERK1／2）表达的影响。方法健康成年雄性SD大鼠48只，体重220～250g，采用随机数字表法，将其随机分为6组（n=8）：正常对照组（c组）、假手术组（S组）、心肌缺血再灌注组（I／R组）和吗啡低、中、高剂量预处理组（MP1-3组）。c组尾静脉注射生理盐水5ml／kg，其余各组给予阿霉素2．0mg／kg，每周1次，共6次，建立慢性心力衰竭模型。于末次给药后14d，采用彩色超声仪测量左心室舒张末期内径（LVEDD）和左心室收缩末期内径（LVESD），计算左心室射血分数（LVEF）和左心室短轴缩短率（LVFS），并取颈动脉血样，测定血浆脑利钠肽（BNP）浓度。于末次给药后16d，采用阻断冠状动脉左前降支30min，再灌注120min制备心肌缺血再灌注模型。S组仅穿线不结扎；MP1-3组分别静脉输注吗啡0．015、0．030、0．050mg／kg，输注5min，停止5min，重复3次，I／R组给予等容量生理盐水。除C组外，其余各组于再灌注120min时处死大鼠，取心脏，测定缺血危险区（AAR）和梗死区（IS）的体积，计算IS／AAR比值，并采用Westernblot法检测心肌p-ERKI／2表达。结果与C组比较，其余各组LVESD升高，LVEF和LVFS降低，血浆BNP浓度升高（P〈0．01）；S组未检测到心肌梗死；与S组比较，I／R组和MP，组心肌p-ERK1／2表达下调（P〈0．05），MP2组及MB组差异无统计学意义（P〉0．05）；与I／R组比较，MR组和MB组IS体积和IS／AAR比值降低，心肌p-ERK1／2表达上调（P〈0．05），MP．组差异无统计学意义（P〉0．05）；MP，组～ME组IS体积和IS／AAR比值逐渐降低，心肌p-ERKI／2表达逐渐上调（P〈0．05）。结论吗啡预处理可减轻慢性心力衰竭大鼠心肌缺血再灌注损伤，且呈剂量依赖性，其机制与上调心肌p-ERK1／2�Objective To investigate the effects of morphine preconditioning on myocardial isehemia- reperfusion （I/R） injury and the expression of phosphorylated extracellular signal-regulated kinase 1/2 （p-ERK1/2） in rats with chronic heart failure. Methods Forty-eight healthy male SD rats weighing 220-250 g were randomly divided into 6 groups （n = 8 each）： control group （group C）, sham operation group （group S）, I/R group and preconditioning with low, median and high doses of morphine groups （groups MP1-3 ） Chronic heart failure was in-duced by iv adriamycin 2.0 mg/kg once a week for 6 weeks in groups S, I/R and MP1-3 Left ventricular end-diastolic diameter （LVEDD） and left ventricular end-systolic diameter （LVESD） were measured using ultrasound, and left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） were calculated at the end of 14th day after the end of adriamycin administration. Blood samples from the carotid artery were collected after ultrasonography for determination of the plasma brain natriuretic peptide （BNP） concentration. Myocardial I/R was induced by 30 min occlusion of left anterior descending branch of coronary artery followed by 120 min reperfusion at 2 day after ultrasonography in groups I/R and MP1-3 . In groups MP1-3 , iv morphine 0.015, 0.030 and 0.050 mg/kg were repeated 3 times at 5 min interval at 30 min before ischemia respectively, while normal saline 5 ml/kg was given in group I/R. The animals were sacrificed at the end of reperfusion in groups S, I/R and MP1-3, and the hearts were removed to measure the area at risk （AAR）, infarct size （IS）, and IS/AAR ratio was calculated. The p-ERK1/2 expression in myocardium was assessed by Western blot. Results The LVESD and plasma BNP concentration were significantly higher, while the LVEF and LVFS lower in the other 5 groups than in group C （ P 〈 0.01 ） . No myocardial infarction was found in group S. The p-ERK1/2 expression was significantly lower in grou

关 键 词：吗啡 缺血预处理 心肌再灌注损伤 心力衰竭 细胞外信号调节MAP激酶类 

分 类 号：R541.6[医药卫生—心血管疾病]