橙皮素对心肌梗死小鼠心室重塑及心肌组织心房钠尿肽和β-肌球蛋白重链表达的影响

Effects of hesperetin on ventricular remodeling and expression of myocardial tissue atrial natriuretic peptide andβ-myosin heavy chain in myocardial infarction mice

目的研究橙皮素对心肌梗死小鼠心室重塑及心肌组织心房钠尿肽(ANP)、β-肌球蛋白重链(β-MHC)表达的影响。方法用左冠状动脉前降支近端结扎法构建心肌梗死小鼠模型。将成功建立的60只心肌梗死小鼠随机分为模型组及低、高剂量实验组,各20只;另选择20只正常小鼠作为对照组。低、高剂量实验组小鼠分别给予10,20 mg·kg^-1·d^-1橙皮素,灌胃,对照组与模型组灌胃等量生理盐水,连续干预8周。用心脏多普勒超声检测左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、左心室射血分数(LVEF)及左心室短轴缩短分数(LVFS)评价心功能;用脱氧核糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)染色观察心肌细胞凋亡指数;用Masson染色观察小鼠心肌纤维化情况;用蛋白质印迹(WB)法检测心肌组织ANP、β-MHC蛋白表达。结果对照组、模型组和低、高剂量实验组小鼠LVEDD分别为(3.18±0.12),(5.46±0.06),(4.87±1.14),(3.93±1.36)mm;LVESD分别为(1.93±0.14),(4.63±1.26),(3.52±1.61),(2.46±0.97)mm;LVEF分别为(82.87±3.15)%,(39.54±2.13)%,(56.22±2.95)%,(71.46±3.08)%;LVFS分别为(46.84±1.56)%,(18.43±1.15)%,(27.63±1.27)%,(40.22±1.39)%;各组小鼠心肌组织ANP蛋白相对表达量分别为0.07±0.02,0.76±0.13,0.48±0.11,0.25±0.08;β-MHC蛋白相对表达量分别为0.27±0.06,0.85±0.12,0.45±0.06,0.40±0.09。与对照组相比,模型组小鼠LVEDD、LVESD与心肌细胞凋亡指数及心肌组织ANP、β-MHC蛋白相对表达量均升高,且低、高剂量实验组低于模型组;LVEF与LVFS降低,且低、高剂量实验组高于模型组,均呈剂量依赖性(均P<0.05)。结论橙皮素可改善心肌梗死小鼠心肌纤维化程度,改善心功能指标,抑制心肌细胞凋亡,同时降低心肌肥厚标记物的表达,进而抑制小鼠心肌梗死后心室重塑并改善心脏功能。

Objective To investigate the effects of hesperetin on ventricular remodeling and expression of myocardial tissue atrial natriuretic peptide(ANP)andβ-myosin heavy chain(β-MHC)in myocardial infarction mice.Methods The mouse models of myocardial infarction were constructed by ligation of the left anterior descending coronary artery.Sixty myocardial infarction mice successfully established were randomly divided into model group and Exp-L,Exp-H groups,20 mice in each group;another 20 normal mice were selected as control group.The mice in Exp-L,Exp-H groups were given mesothelin 10 and 20 mg·kg^-1·d^-1,control group and model group were given the same amount of normal saline for 8 weeks.Cardiac function was evaluated by cardiac doppler ultrasonography for left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF),and left ventricular fraction shortening(LVFS).cardiomyocyte apoptotic index was observed by TUNEL staining;myocardial fibrosis was observed by Masson staining.The expression of ANP andβ-MHC protein in myocardial tissues were detected by Western blotting(WB)method.Results The LVEDD in control group,model group and Exp-L,Exp-H groups were(3.18±0.12),(5.46±0.06),(4.87±1.14)and(3.93±1.36)mm;LVESD were(1.93±0.14),(4.63±1.26),(3.52±1.61),(2.46±0.97)mm;LVEF were(82.87±3.15)%,(39.54±2.13)%,(56.22±2.95)%,(71.46±3.08)%;LVFS were(46.84±1.56)%,(18.43±1.15)%,(27.63±1.27)%,(40.22±1.39)%;the relative expression levels of ANP protein in myocardial tissues were0.07±0.02,0.76±0.13,0.48±0.11,0.25±0.08,the relative expression levels ofβ-MHC protein were0.27±0.06,0.85±0.12,0.45±0.06 and 0.40±0.09.Compared with control group,the LEVDD,LVESD and cardiomyocyte apoptotic index and the relative expression of ANP andβ-MHC protein increased in model group,and Exp-L,Exp-H groups were lower than model group;LVEF and LVFS reduced,and Exp-L,Exp-H groups were higher than model group,and was dose-dependent(all P<0.05).Conclusion Hesperetin can improve the degree of myocardial fibrosis in mice with myocardial infarction,improve cardiac function,inhibit cardiomyocyte apoptosis,and reduce the expression of cardiac hypertrophic markers,thereby inhibiting ventricular remodeling and improving cardiac function after myocardial infarction in mice.