ABSTRACT
OBJECTIVE@#To explore the impact of electroacupuncture (EA) on the AMPKα-HDAC5-HIF-1α signaling in the heart of the rats with myocardial ischemia (MI) via detecting the expressions of AMP-activated protein kinase α (AMPKα), histone deacetylase 5 (HDAC5), hypoxia inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF).@*METHODS@#Thirty-six healthy male SD rats were randomized into a sham operation group (6 rats), a sham + EA group (6 rats), a model group (12 rats) and an EA group (12 rats). We ligated the left anterior descending artery (LAD) for MI model, and exposed the heart of rats after opening the chest without ligation for the rats in the sham operation gorup and the sham + EA group. On the 2nd day after LAD ligation, EA was applied at "Neiguan" (PC 6) with 2 Hz/15 Hz and 1.5-2 mA for 30 min in the EA group and sham+EA group, once a day for 4 days. The same fixation was used in the sham operation group and the model group, without EA. Myocardial infarction area was observed by TTC staining and serum cardiac troponin T (cTnT) was detected by radioimmunoassay. The expression of VEGF mRNA was detected by real time PCR. The protein expressions of AMPKα, HDAC5, HIF-1α and VEGF were detected by western blot.@*RESULTS@#Compared with the sham operation group, 4 days after LAD ligation, the myocardial infarction was obvious and the expression of serum cTnT increased in the model group (0.05). After EA for 4 days, the myocardial infarction area and cTnT expression decreased in the EA group (both <0.01); the VEGF mRNA and protein expressions and AMPKα, HDAC5, HIF-1α protein expressions increased (<0.05, <0.01).@*CONCLUSION@#EA could regulate the AMPKα-HDAC5-HIF-1α signaling in myocardial tissue, which may activate VEGF expression for angiogenesis signaling, reduce myocardial infarction area so as to achieve cardioprotective effect.
Subject(s)
Animals , Male , Rats , AMP-Activated Protein Kinases , Electroacupuncture , Histone Deacetylases , Hypoxia-Inducible Factor 1, alpha Subunit , Myocardial Ischemia , Rats, Sprague-Dawley , Signal Transduction , Vascular Endothelial Growth Factor AABSTRACT
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
3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, produces rapid antidepressant-like effects in animal models of depression. However, the molecular mechanisms underlying these behavioral actions remain unknown. Here, we demonstrate that CPP rapidly stimulates histone deacetylase (HDAC) 5 phosphorylation and nuclear export in rat hippocampal neurons. These effects are accompanied by calcium/calmodulin kinase II (CaMKII) and protein kinase D (PKD) phosphorylation. Behavioral experiments revealed that viral-mediated hippocampal knockdown of HDAC5 blocked the antidepressant effects of CPP in stressed animals. Taken together, our results imply that CPP acts via HDAC5 and suggest that HDAC5 is a common regulator contributing to the antidepressant actions of NMDA receptor antagonists such as CPP.