CAJ | 학술논문

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220～250 g,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5 ml/kg,其余各组给予阿霉素2.0 mg/kg,每周1次,共6次,建立慢性心力衰竭模型.于末次给药后14 d,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16 d,采用阻断冠状动脉左前降支30 min,再灌注120 min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、0.050 mg/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120 min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Western blot法检测心肌p-ERK1/2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MP1组心肌p-ERK1/2表达下调(P＜0.05),MP2组及MP3组差异无统计学意义(P＞0.05)；与I/R组比较,MP2组和MP3组IS体积和IS/AAR比值降低,心肌p-ERK1/2表达上调(P＜0.05),MP1组差异无统计学意义(P＞0.05)；MP1组～MP3组IS体积和IS/AAR比值逐渐降低,心肌p-ERK1/2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表达有关.
목적 탐토마배예처리대만성심력쇠갈대서심기결혈재관주손상급심기린산화세포외신호조절격매1/2(p-ERK1/2)표체적영향.방법 건강성년웅성SD대서48지,체중220～250 g,채용수궤수자표법,장기수궤분위6조(n=8):정상대조조(C조)、가수술조(S조)、심기결혈재관주조(I/R조)화마배저、중、고제량예처리조(MP1-3조).C조미정맥주사생리염수5 ml/kg,기여각조급여아매소2.0 mg/kg,매주1차,공6차,건립만성심력쇠갈모형.우말차급약후14 d,채용채색초성의측량좌심실서장말기내경(LVEDD)화좌심실수축말기내경(LVESD),계산좌심실사혈분수(LVEF)화좌심실단축축단솔(LVFS),병취경동맥혈양,측정혈장뇌리납태(BNP)농도.우말차급약후16 d,채용조단관상동맥좌전강지30 min,재관주120 min제비심기결혈재관주모형.S조부천선불결찰；MP1 -3조분별정맥수주마배0.015、0.030、0.050 mg/kg,수주5min,정지5min,중복3차,I/R조급여등용량생리염수.제C조외,기여각조우재관주120 min시처사대서,취심장,측정결혈위험구(AAR)화경사구(IS)적체적,계산IS/AAR비치,병채용Western blot법검측심기p-ERK1/2표체.결과 여C조비교,기여각조LVESD승고,LVEF화LVFS강저,혈장BNP농도승고(P＜0.01)；S조미검측도심기경사；여S조비교,I/R조화MP1조심기p-ERK1/2표체하조(P＜0.05),MP2조급MP3조차이무통계학의의(P＞0.05)；여I/R조비교,MP2조화MP3조IS체적화IS/AAR비치강저,심기p-ERK1/2표체상조(P＜0.05),MP1조차이무통계학의의(P＞0.05)；MP1조～MP3조IS체적화IS/AAR비치축점강저,심기p-ERK1/2표체축점상조(P＜0.05).결론 마배예처리가감경만성심력쇠갈대서심기결혈재관주손상,차정제량의뢰성,기궤제여상조심기p-ERK1/2표체유관.
Objective To investigate the effects of morphine preconditioning on myocardial ischemiareperfusion (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 induced by iv edriamycin 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 groups I/R and MP1 than in group S (P ＜ 0.05).IS and IS/AAR ratio were significantly lower,and p-ERK1/2expression was significantly higher in groups MP2.3 than in group I/R ( P ＜ 0.05).There were no significant differences in IS,IS/AAR ratio and p-ERK1/2 expression between groups MP1 and I/R (P ＞ 0.05).IS and IS/AAR ratio were decreased gradually,and the p-ERK1/2 expression was up-regulated gradually in groups MP1-3 ( P ＜0.05).Conclusion Morphine preconditioning can confer cardioprotection against myocardial I/R in a dose-dependent manner in rats with chronic heart failure.Up-regulation of p-ERK1/2 expression is involved in the underlying mechamism.