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Protein kinase A-mediated cardioprotection of Tongxinluo relates to the inhibition of myocardial inflammation, apoptosis, and edema in reperfused swine hearts / 中华医学杂志(英文版)
Chinese Medical Journal ; (24): 1469-1479, 2013.
Article Dans Anglais | WPRIM | ID: wpr-350486
ABSTRACT
<p><b>BACKGROUND</b>Our previous studies have demonstrated that Tongxinluo (TXL), a traditional Chinese medicine, can protect hearts against no-reflow and reperfusion injury in a protein kinase A (PKA)-dependent manner. The present study was to investigate whether the PKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis.</p><p><b>METHODS</b>In a 90-minute ischemia and 3-hour reperfusion model, minipigs were randomly assigned to sham, control, TXL (0.05 g/kg, gavaged one hour prior to ischemia), and TXL + H-89 (a PKA inhibitor, intravenously and continuously infused at 1.0 µg/kg per minute) groups. Myocardial no-reflow, necrosis, edema, and apoptosis were determined by pathological and histological studies. Myocardial activity of PKA and myeloperoxidase was measured by colorimetric method. The expression of PKA, phosphorylated cAMP response element-binding protein (p-CREB) (Ser(133)), tumor necrosis factor α (TNF-α), P-selectin, apoptotic proteins, and aquaporins was detected by Western blotting analysis.</p><p><b>RESULTS</b>TXL decreased the no-reflow area by 37.4% and reduced the infarct size by 27.0% (P < 0.05). TXL pretreatment increased the PKA activity and the expression of Ser(133) p-CREB in the reflow and no-reflow myocardium (P < 0.05). TXL inhibited the ischemia-reperfusion-induced elevation of myeloperoxidase activities and the expression of TNF-α and P-selectin, reduced myocardial edema in the left ventricle and the reflow and no-reflow areas and the expression of aquaporin-4, -8, and -9, and decreased myocytes apoptosis by regulation of apoptotic protein expression in the reflow and no-reflow myocardium. However, addition of the PKA inhibitor H-89 counteracted these beneficial effects of TXL.</p><p><b>CONCLUSION</b>PKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis in the reflow and no-reflow myocardium.</p>
Sujets)
Texte intégral: Disponible Indice: WPRIM (Pacifique occidental) Sujet Principal: Pharmacologie / Physiologie / Suidae / Porc miniature / Médicaments issus de plantes chinoises / Lésion de reperfusion myocardique / Protéine de liaison à l&apos;élément de réponse à l&apos;AMP cyclique / Apoptose / Cyclic AMP-Dependent Protein Kinases / Oedème Type d'étude: Étude pronostique Limites du sujet: Animaux langue: Anglais Texte intégral: Chinese Medical Journal Année: 2013 Type: Article

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Texte intégral: Disponible Indice: WPRIM (Pacifique occidental) Sujet Principal: Pharmacologie / Physiologie / Suidae / Porc miniature / Médicaments issus de plantes chinoises / Lésion de reperfusion myocardique / Protéine de liaison à l&apos;élément de réponse à l&apos;AMP cyclique / Apoptose / Cyclic AMP-Dependent Protein Kinases / Oedème Type d'étude: Étude pronostique Limites du sujet: Animaux langue: Anglais Texte intégral: Chinese Medical Journal Année: 2013 Type: Article