曲美他嗪对小鼠急性心肌缺血再灌注损伤的保护作用

Effect of trimetazidine on protecting against acute myocardial ischemia/reperfusion injury in mice

目的探讨早期应用曲美他嗪对小鼠急性心肌缺血再灌注损伤的保护作用。方法 C57/BL6小鼠40只,随机分为对照组、假手术组、曲美他嗪组和模型组各10只。曲美他嗪组和模型组结扎冠状动脉前降支,缺血30min后再灌注,假手术组只穿线不结扎,对照组不作任何处理。再灌注前5min,假手术组和曲美他嗪组尾静脉注射曲美他嗪1mg/kg,模型组注射等体积生理盐水;术后第2天,假手术组和曲美他嗪组给予曲美他嗪15mg/(kg·d)灌胃持续30d,模型组给予等体积生理盐水灌胃;对照组不作任何处理。再灌注30d后4组小鼠行超声心动图检查,处死小鼠后取出心脏,制成7μm和3μm切片,分别行Masson染色和麦胚凝集素染色,观察心肌细胞横断面面积(myocardial cross-sectional area,MCSA)和左心室膨展指数(index of expansion,IE)。结果对照组、假手术组和曲美他嗪组左室射血分数(left ventricular ejection fraction,LVEF)[(54.14±3.56)%、(47.03±4.47)%、(40.20±6.12)%]、短轴缩短率(fractional shortening,FS)[(25.07±3.85)%、(20.53±3.40)%、(20.28±3.61)%]及左心室室壁厚度(left ventricular wall thickness,LVWT)[(0.78±0.06)、(0.77±0.03)、(0.76±0.05)mm]均大于模型组[(32.82±3.98)%、(14.98±1.91)%、(0.69±0.04)mm](P<0.05),左心室收缩末期容积(left ventricular end-systolic volume,LVESV)[(32.93±7.67)、(34.49±10.86)、(38.68±5.98)μL]及左心室舒张末期容积(left ventricular end-diastolic volume,LVEDV)[(59.43±8.65)、(59.14±13.52)、(63.36±9.92)μL]小于模型组[(49.18±6.19)、(77.67±7.22)μL](P<0.05);对照组LVEF大于曲美他嗪组(P<0.05),FS、LVESV、LVEDV、LVWT与假手术组和曲美他嗪组比较差异无统计学意义(P>0.05),假手术组LVEF、FS、LVESV、LVEDV、LVWT与曲美他嗪组比较差异无统计学意义(P>0.05);对照组、假手术组和曲美他嗪组心肌细胞MCSA[(237.61±11.28)、(248.13±40.63)、(300.98±29.23)μm^2]小于模型组[(396.55±74.75)μm^2],IE(0.16±0.06、0.17±0.05、0.21±0.05)低于模型组(0.31±0.09)(P<0.05),对照组、假手术组、曲美他嗪组心肌细胞MCSA、IE比较差异无统计学意义(P>0.05)。结论急性心肌缺血再灌注损伤小鼠早期应用曲美他嗪可降低心室重构,改善左心室功能,对缺血再灌注导致的心肌损伤具有保护作用。

Objective To explore the effect of early administration of trimetazidine(TMZ)on protecting against acute myocardial ischemia/reperfusion(I/R)injury in mice.Methods Forty C57/BL6 mice were randomly divided control group,sham operation group,TMZ group and model group,with 10 mice in each group.The coronary artery was ligated and given reperfusion after ischemia for 30 min in TMZ group and model group.Sham operation group was performed threading but no ligation.Control group received no treatment.Five min before reperfusion,sham operation group and TMZ group were intravenously injected TMZ(1mg/kg)via tail vein,model group was given equivalent volume of normal saline.From the second day after operation,sham operation group and TMZ group were given gavage by 15mg/(kg·d)TMZ for 30 days,model group was given equivalent volume of normal saline,and control group received no treatment.After 30 dreperfusion,all these 4groups received echocardiography.The heart of mice was taken to make 7 and 3μm slices after sacrificed and underwent Masson staining and wheat germ agglutinin staining to observe the myocardial crosssectional area(MCSA)and left ventricular index of expansion(IE).Results The left ventricular ejection fraction(LVEF)((54.14±3.56)%,(47.03±4.47)%,(40.20±6.12)%),fractional shortening(FS)((25.07±3.85)%,(20.53±3.40)%,(20.28±3.61)%)and left ventricular wall thickness(LVWT)((0.78±0.06),(0.77±0.03),(0.76±0.05)mm)in control group,sham operation group and TMZ group were significantly higher than those in model group((32.82±3.98)%,(14.98±1.91)%,(0.69±0.04)mm)(P<0.05),left ventricular end-systolic volume(LVESV)((32.93±7.67),(34.49±10.86),(38.68±5.98)μL)and left ventricular end-diastolic volume(LVEDV)((59.43±8.65),(59.14±13.52),(63.36±9.92)μL)in control group,sham operation group and TMZ group were significantly lower than those in model group((49.18±6.19),(77.67±7.22)μL)(P<0.05),LVEF was significantly higher in control group than that in TMZ group(P<0.05),FS,LVESV,LVEDV and LVWT in control group showed no significant differences in comparison with those in sham operation group and TMZ group(P>0.05),and LVEF,FS,LVESV,LVEDV and LVWT in sham operation group showed no significant differences in comparison with those in TMZ group(P>0.05).The MCSA((237.61±11.28),(248.13±40.63),(300.98±29.23)μm^2)and left ventricular index of expansion(IE)(0.16±0.06,0.17±0.05,0.21±0.05)in control group,sham operation group and TMZ group were significantly smaller than those in model group((396.55±74.75)μm2,0.31±0.09)(P<0.05),and there were no significant differences in control group,sham operation group and TMZ group(P>0.05).Conclusion The early application of TMZ can protect against myocardial I/R injury in mice by reducing the ventricular remodeling and improving the left ventricular function.