| BackgroundAcute myocardial infarction(AMI)occurs when there is a stenosis or blockage in a coronary artery,resulting in adjacent myocardial ischemia.The consequent malignant arrhythmia,cardiogenic shock or heart failure remain to be leading causes of death and disability around the world.Ventricular remodeling is one of the main pathophysiologic changes after myocardial infarction.The situation will worsen when there is a lack of angiogenesis.The structural remodeling can eventually contribute to the severity of heart failure.It is well acknowledged that angiotensin converting enzyme inhibitors(ACEI)remarkably improve the prognosis of AMI,with the accurate mechanism remained unknown.Astragaloside IV(AS-IV)is a major active ingredient derived from Astragalus Membranaceus Bunge,a herb widely used for cardiovascular diseases in traditional Chinese medicine.It has been shown to protect myocardium from ischemic injury by surpressing cardiac hypertrophy,maintaining calcium transport,and enhancing antioxidative capacity.We have previously demonstrated that AS-IV could stimulate angiogenesis so as to improve post-infarction healing in mice.Here,we aim to investigate the impact of treatment of AS-IV combined with Enalapril in mice post infarction.ObjectiveTo investigate the effects of astragaloside IV combined with enalapril on cardiac function and angiogenesis in acute myocardial infarction mice.Methods1.The mice model of acute myocardial infarction and experimental groups.24 eight-week-old male C57BL/6 mice were randomly divided into 4 groups averagely: group Sham,group CTL,group Enalapril,and group AS-IV+Enalapril.Their body mass ranged from 23.9 to 29.2 g.The left anterior descending coronary artery(LAD)of the coronary artery was observed under the stereoscopic microscope.Mice in group CTL,group Enalapril,and group AS-IV+Enalapril were ligated with 6-0 nylon ligation line in the lower left atrial appendage to ligate LAD,and the Sham group was not ligated and the chest was sutured immediately.2.Treatment of the mice.The Sham group and CTL group were injected intraperitoneally and intragastric filled by with saline.Group Enalapril was injected with saline intraperitoneally and intragastric filled by Enalapril.Group ASIV+Enalapril was intraperitoneally injected with AS-IV and intragastric filled by Enalapril.Normal saline and enalapril were administered through intragastric administration by 7.5 mg/kg,and astragaloside IV(1mg/ml,HPBCD soluble)and saline were injected intraperitoneally by 10 mg/kg.The treatment sustained 2 weeks.3.Examination of cardiac function.The heart function of the mice was examined by echocardiography after 2 weeks of treatment.4.Observation of cardiac morphology.After the end of the ultrasound examination,the mice were killed and the heart was immediately taken and weighed.The weight of left ventricle was recorded.5.HE and Masson staining.After embedded with the paraffin the paraffin was embedded,the heart was sliced from the apex until the infarcted myocardium appeared.The 3 um slices were sectioned to the location far away from the infarct area.The slices were stained with HE and Masson,and the pathological changes were observed under the microscope.The remaining tissue were stored at-80 C after the OCT embedment.6.Immunofluorescence staining.The blood vessel density and angiogenesis were observed with CD31/ VEGFR3 double-immunofluorescence staining.Results1.Cardiac function.Compared with group Sham,the left ventricular ejection fraction(EF%)and fractional shortening(FS%)in group CTL were significantly decreased(P < 0.05)at 2 weeks after AMI.Compared with group CTL,the heart function of group Enalapril was significantly improved(P < 0.05).The cardiac function of group AS-IV+Enalapril was better than group Enalapril(P < 0.05).2.The heart weight index(HW/BW).The heart weight versus body weight ratio(HW/BW)of group CTL was significantly higher than that of group Sham(P < 0.05).HW/BW of group Enalapril and group AS-IV+Enalapril were significantly bigger than group CTL(P < 0.05).There is no significant difference between group ASIV+Enalapril and group Enalapril.3.HE staining and Masson staining.The results showed that the heart tissue of group CTL were significantly infiltrated with inflammatory cells and had a high level of fibrosis,and the heart tissues of Enalapril and AS-IV+Enalapril groups had less inflammatory cells and fibrosis than group CTL.4.Immunofluorescence staining.CD31/ VEGFR3 double immunofluorescence staining showed that compared with group CTL,the density of blood vessels in the infarct border zone of group Enalapril and AS-IV+Enalapril group was higher.The ratio of neovascularization was higher,and the group AS-IV+Enalapril was superior to that of the Enalapril group.ConclusionsAstragaloside IV combined with enalapril can effectively improve cardiac function in acute myocardial infarction mice and promote angiogenesis in the border area of myocardial infarction. |
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