ABSTRACT
OBJECTIVE This study aimed to investigate the role and mechanism of Astragaloside IV (AS-IV)in rats with myocardial infarction.METHODS The myocardial infarction model was established by ligation of the left anterior descending artery. The rats were randomly divided into sham, DMSO, model group, AS-IV and CID755673 groups. The rats were sacrificed 4 weeks later, and segmental heart samples were used for hematoxylin and eosin staining and masson staining. The expression of PKD1, HDAC5 and VEGF were analyzed using immunohistochemistry, reverse transcription poly-merase chain reaction and western blot. RESULTS Compared with the sham operation and DMSO groups,morphology of myocardium in model group was disordered,accompanied with necrotic myocar-dial cells and obvious collagen tissues. After treatment with AS-IV, the morphology of myocardium was obviously improved, and the number of new blood vessels increased significantly. However, after treatment with CID755673, the myocardial tissue of rats became disordered again, the necrotic cells increased, and some vessels closed. The expression levels of PKD1, HDAC5 and VEGF mRNA and protein in myocardial tissue of model group were significantly lower than the other four groups(P<0.05), whereas these levels in the AS-IV group were significantly higher than those in the other four groups (P<0.01). Additionally, the CID755673 group had significantly higher levels of PKD1, HDAC5 and VEGF mRNA and protein than the sham group, DMSO group and model group (P<0.05). CONCLUSION AS-IV may partly promote the angiogenesis of myocardial tissue in rats with myocardial infarction via the PKD1-HDAC5-VEGF pathway.
ABSTRACT
AIM:To investigate the angiogenic effect and mechanisms of astragaloside IV(AS-IV)in rats with myocardial infarction via protein kinase D 1(PKD1)-histone deacetylase 5(HDAC5)-vascular endothelial growth factor (VEGF)signaling pathway.METHODS:The classic model of myocardial infarction by ligation of the left anterior de-scending coronary artery was replicated,and the rats were randomly divided into model group,AS-IV group,and AS-IV+CID755673(PKD1 inhibitor)group.The sham operation control group and DMSO control group were also set up.All the rats were given intravenous injection via caudal vein.The rats were sacrificed 4 weeks later,and segmental heart samples were used for HE staining and Masson staining.The expression of PKD1,HDAC5 and VEGF was analyzed by immunohis-tochemistry,RT-PCR and and Western blot.RESULTS:Compared with sham operation group and DMSO group,the myo-cardium in model group showed disordered arrangement, accompanied with necrotic myocardial cells and obvious fibrosis tissue.After treatment with AS-IV,the morphological changes of myocardium were obviously improved,and the number of new blood vessels increased significantly.However,after treatment with AS-IV+CID755673,the myocardial tissues of the rats became disordered again,with increased necrotic cells and some closed vessels.The mRNA and protein expression of PKD1,HDAC5 and VEGF in myocardial tissue in model group was significantly lower than that in sham operation and DMSO groups(P<0.05).The expression in AS-IV group was significantly higher than that in model group(P<0.01), while that in AS-IV+CID755673 group was significantly lower than that in AS-IV group(P<0.05).CONCLUSION:AS-IV promotes the angiogenesis of myocardial tissues in the rats after myocardial infarction partly by regulating the PKD 1-HDAC5-VEGF signaling pathway.