RESUMEN
Madecassoside (MA), one of the principle terpenoids in Centella asiatica, has shown protect effect on isolated rat hearts and isolated cardiomyocytes against reperfusion injury in our previous studies. The aim of this study is to investigate if MA also protected against myocardial ischemia-reperfusion injury in vivo. The ischemia infarction model was established in rats. Left ventricular function was monitored during the ischemia-reperfusion period by a multi-channel recorder. After the ischemia-reperfusion process the infarcted areas were assessed. The levels of lactate dehydrogenase (LDH), creatinephosphokinase (CK), malondialdehyde (MDA), super-oxide dismutase (SOD) and C-reactive protein (CRP) in serum were determined. Cardiomyocytic apoptosis was measured by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining. Pre-treatment with MA (50, 10 mg/kg) attenuated myocardial damage characteristic of decreasing infarct size, decreasing LDH and CK release. Activities of SOD were increased and MDA level increased obviously in control group whereas pretreatment with MA blunted the decrease of SOD activity, markedly reduced the level of MDA and the activity of CRP, and relieved myocardial cell apoptosis. These results suggest that MA has the protective effect on myocardial ischemia-reperfusion injury. This protection ability possibly due to its anti-lipid peroxidation, anti-inflammation and anti-apoptosis function and the enhancement of SOD activity.
Asunto(s)
Cardiotónicos/uso terapéutico , Infarto del Miocardio/prevención & control , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Triterpenos/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Cardiotónicos/aislamiento & purificación , Cardiotónicos/farmacología , Centella/química , Hemodinámica/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Estructura Molecular , Infarto del Miocardio/etiología , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Daño por Reperfusión Miocárdica/complicaciones , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/fisiopatología , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Triterpenos/aislamiento & purificación , Triterpenos/farmacología , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
This study is to investigate if madecassoside can protect against myocardial reperfusion injury in rabbit heart in vivo. The ischemia reperfusion model was established. Left ventricular function and ECG were monitored at the ischemia and reperfusion period. The infarct areas were expressed as percentage. The levels of LDH, CK, MDA and SOD were measured and C-reactive protein (CRP) in serum was measured by ELISA kit. Cardiomyocyte apoptosis were measured by TUNEL staining. A monoclonal rabbit anti-goat Bcl-2 proteins as primary antibody was used for Bcl-2 immunohistochemical staining. Treatment with madecassoside (3.2, 1.6 and 0.8 mg x kg(-1)) i.v. during ischemia reperfusion injury attenuated myocardial damage, that is, characteristic of decreasing infarct size, decreasing LDH and CK release. Activities of SOD were diminished and MDA level increased obviously in control group whereas pretreatment with madecassoside significantly blunted the decrease of SOD activity, markedly reduced the levels of MDA, CRP and cardiomyocyte apoptosis, and upregulated the expression of Bcl-2. Madecassoside has the protective effect against myocardial ischemia reperfusion injury, and effects of anti-lipid peroxidation, enhancement of SOD activity, anti-inflammation and anti-apoptosis.