RESUMEN
BACKGROUND/AIMS: In this study, we examined whether the combination of hyperbaric oxygen (HBO) and diltiazem therapy provided a cardioprotective effect on myocardial ischemia-reperfusion injury (MIRI) rat model. METHODS: Sixty healthy Sprague-Dawley rats were randomly divided into sham, IR, diltiazem (5 mg/kg), HBO (0.25 MPa, 60 min) and combination therapy (HBO plus diltiazem) groups. MIRI model was established by ligating the left anterior descending for 30 min, followed by 60 min of reperfusion. RESULTS: The results show that HBO and diltiazem preconditioning significantly improves cardiac function and myocardial infarction area, increases nitric oxide, endothelial nitric oxide synthase and ATPase (Na+-K+-ATPase and Ca2+-Mg2+-ATPase) activity and decreases levels of oxygen stress, myocardial enzymes and endothelin-1. Notably, HBO and diltiazem preconditioning significantly increased Bcl-2 protein expression and decreased Bax protein and caspase-3 mRNA expression. CONCLUSIONS: These data indicate that combination therapy protected against heart MIRI by reducing oxygen stress damage, correcting energy metabolism, improving endothelial function and inhibiting cell apoptosis.
Asunto(s)
Diltiazem/uso terapéutico , Oxigenoterapia Hiperbárica , Daño por Reperfusión Miocárdica/terapia , Sustancias Protectoras/uso terapéutico , Animales , Caspasa 3/genética , Caspasa 3/metabolismo , Terapia Combinada , Diltiazem/farmacología , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Endotelina-1/genética , Endotelina-1/metabolismo , Femenino , Corazón/diagnóstico por imagen , Precondicionamiento Isquémico , Masculino , Infarto del Miocardio , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Sustancias Protectoras/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Sprague-Dawley , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Five new flavonoid glycosides, namely nervilifordins F-J (1-5), were isolated from the 60% EtOH extract of the aerial parts of Nervilia fordii, along with three first isolated flavonoids (7, 8, and 13) and five known flavonoids (6, 9-12). The structures of new compounds were elucidated on the basis of 1D and 2D NMR and MS studies. Their anti-inflammatory activities were tested by measuring their inhibitory effects on nitric oxide production in lipopolysaccharide-activated RAW264.7 macrophages. Compounds 2 and 5 showed interesting inhibition effects with their EC50 values of 15.15 µM and 14.80 µM, respectively.