橙皮素干预改善小鼠心肌梗死后心室重构及心功能
Role of hesperetin intervention on cardiac function and ventricular remodeling after myocardial infarction
王冰 1李良海 2金平 2李建国1
作者信息
- 1. 430071武汉,武汉大学中南医院重症医学科
- 2. 434020湖北省荆州,长江大学第二临床医学院荆州市中心医院重症医学科
- 折叠
摘要
目的 观察橙皮素对小鼠心肌梗死后心室重构及心功能的影响.方法 采用左前降支结扎术制备心肌梗死模型,42只C57BL/6小鼠随机(随机数字法)分为假手术组和心肌梗死组,术后24 h存活小鼠随机(随机数字法)分为心肌梗死对照组和橙皮素治疗组.术后8周,血流动力学测定及超声心动图评估心功能及心脏结构改变;苏木精-伊红染色观察心肌细胞横截面积(CSA)、天狼星红染色观察胶原蛋白沉积并计算胶原容积分数(CVF)、RT-PCR检测心肌肥厚标志物心房钠尿肽(ANP)、脑钠尿肽(BNP)及β-肌球蛋白重链(β-MHC)、心肌纤维化标志物胶原蛋白Ⅰ、胶原蛋白Ⅲ及结缔组织生长因子(CTGF)的表达.比色法测定心肌组织中超氧阴离子及羟自由基的含量.多组间差异比较采用单因素方差分析.结果 与假手术组比较,心肌梗死对照组小鼠的左室后壁厚度(LVPWT)和室间隔厚度(IVST)增厚、左室短轴缩短率(LVFS)及左室射血分数(LVEF)显著降低、左室压力上升下降最大速率(±dp/dtmax)显著降低(P＜0.05).与心肌梗死对照组比较,橙皮素干预后LVPWT[(2.29±0.05) mm和(2.85 ±0.10) mm]和IVST[(1.44±0.09) mm和(1.89 ±0.06) mm]变薄;LVFS[(29.48±3.87)％和(20.69±3.99)％]、LVEF[(46.40±1.68)％和(30.51±1.17)％]及±dp/dtmax[(3 344.33±269.57)mmHg/S和(2 205.19±224.17) mmHg/S、(-2 250.40±218.35)mmHg/S和(-1 566.91±217.37) mmHg/S]升高(P＜0.05).与假手术组比较,心肌梗死对照组小鼠的CSA及CVF显著升高;而与心肌梗死对照组比较,橙皮素治疗后可显著降低CSA和CVF (P ＜0.05).与假手术组比较,心肌梗死对照组小鼠的心肌肥厚、心肌纤维化标志物的mRNA表达水平显著升高;而与心肌梗死对照组比较,橙皮素干预后可显著降低心肌肥厚和心肌纤维化标志物的表达(P＜0.05).此外,与心肌梗死对照组比较,橙皮素干预后可显著降低心肌组织中超氧阴离子及羟自由基的含量(P＜0.05).结论 橙皮素可能通过抑制活性氧物质(ROS)的产生,从而抑制心肌梗死后心室重构并改善血流动力学和心脏功能.
Abstract
Objective To explore the effect of hesperidin on cardiac function and ventricular remodeling following myocardial infarction (MI) in mice.Methods Ligation of left anterior descending (LAD) was operated to establish MI model.Forty-two C57BL/6 mice were randomly (random number) divided into control and MI group;and 24 h after LAD ligation,mice in MI group were further divided into MI control and hesperetin group.Eight weeks later,cardiac function and structure changes were determined by the methods of hemodynamic measurement and echocardiography.HE staining was used to measure crosssectional area (CSA) of atrial myocytes,and PSR staining was applied for observe collagen deposition and calculation of collagen volume fraction (CVF).Real-time PCR was used to detect the mRNA expressions of cardiac hypertrophy markers (ANP,BNP and β-MHC) and cardiac fibrosis markers (Collagen Ⅰ,Collagen Ⅲ and CTGF).The contents of superoxide anion and hydroxy radical were detected by colorimetric method.Results Compared with control group,left ventricular posterior wall thickness (LVPWT) and interventricular septum thickness (IVST) were increased to be thicker,left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) were significantly lower,and ± dp/dtmax was remarkably reduced in MI control group (P ＜ 0.05).Compared with MI control group,hesperetin could increaseLVFS [(29.48±3.87)％ vs.(20.69±3.99) ％],LVEF [(46.40±1.68)％ vs.(30.51± 1.17) ％] and ±dp/dtmax [(3 344.33 ±269.57) mmHg/S vs.(2 205.19 ±224.17) mmHg/S;(2250.40±218.35) mmHg/S vs.(-1 566.91 ±217.37) mmHg/S];but could reduce LVPWT [(2.29±0.05) mm vs.(2.85±0.10)mm]andIVST[(1.44±0.09) mm vs.(1.89±0.06) mm].Compared with control group,CSA and CVF were significantly increased in MI control mice.However,hesperetin could reduce CSA and CVF.Compared with control group,the mRNA expressions of cardiac hypertrophy and cardiac fibrosis markers were significantly increased in MI control mice;but hesperetin could significantly inhibit the mRNA expressions of cardiac hypertrophy and cardiac fibrosis markers.Additionally,hesperetin could significantly reduce the contents of superoxide anion and hydroxy radical.Conclusion Hesperetin intervention can inhibit ventricular structure change,and improve hemodynamics and cardiac function after acute myocardial infarction via inhibiting the production of reactive oxygen species (ROS).
关键词
橙皮素/心肌梗死/心功能/心室重构/活性氧物质/小鼠Key words
Hesperetin/Myocardial infarction/Cardiac function/Ventricular remodeling/Reactive oxygen species/Mice引用本文复制引用
出版年
2017
NETL
NSTL
维普
万方数据