RESUMEN
IMPACT STATEMENT: There are about 425 million diabetes patients (20-79 years) in the world according to the International Diabetes Federation Diabetes Atlas - 8th Edition. The cardiovascular complication is one of the major causes of death in diabetes patients. Myocardial fibrosis is one of the serious pathological changes, so investigating the pathogenesis of myocardial fibrosis has the significant value. Our study aims to investigate the effect of Irbesartan (the angiotensin II receptor antagonist) on the changes of AGE-RAGE system and MMP family components, and analyzes the potential mechanisms in type 2 diabetes-induced myocardial fibrosis. Our results provide the theoretical base for better understanding the pathogenesis in type 2 diabetes-induced myocardial complication. It is useful for clinicians to select the effective therapeutic measures for treatment of type 2 diabetes-induced organ fibrosis.
Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Cardiomiopatías Diabéticas/tratamiento farmacológico , Productos Finales de Glicación Avanzada/metabolismo , Irbesartán/uso terapéutico , Metaloproteinasas de la Matriz/metabolismo , Animales , Glucemia/análisis , Peso Corporal , Colágeno/metabolismo , Diabetes Mellitus Tipo 2/etiología , Cardiomiopatías Diabéticas/etiología , Dieta Alta en Grasa/efectos adversos , Fibrosis , Corazón/efectos de los fármacos , Insulina/sangre , Irbesartán/farmacología , Masculino , Miocardio/metabolismo , Miocardio/patología , Ratas , Ratas Sprague-Dawley , Inhibidor Tisular de Metaloproteinasa-2/metabolismoRESUMEN
<p><b>OBJECTIVE</b>To investigate the changes of aldehyde dehydrogenase 2 (ALDH2) expression in H O inducedcardiomyocytes oxidative stress injury.</p><p><b>METHODS</b>Cultured H9C2 cardiomyocytes were exposed to H O -inducedoxidative stress and the effects of the ALDH2 agonist Alda-1 and ALDH2 inhibitor Daidzin were tested on the stress level ofthe exposed cells. MTT colorimetric assay was used to assess the cell viability after the treatments. The oxidative stress level inthe myocardial cells was detected using DHE fluorescence staining, and the activity and protein level of ALDH2 were detectedwith spectrophotometry and Western blotting.</p><p><b>RESULTS</b>Compared with normal control cells, Alda-1 treatment did notsignificantly affect the cell viability, oxidative stress level, or ALDH2 activity and protein level. H O exposure significantlylowered the cell activity and ALDH2 activity and protein expression and increased the oxidative stress level; Alda-1 treatmentobvious antagonized the effects of H O . Blocking ALDH2 with Daidzin produced similar effects to H O exposure on theviability, oxidative stress level, and ALDH2 activity and expression in the myocardial cells.</p><p><b>CONCLUSIONS</b>H O exposure lowersthe activity and reduces the protein expression of ALDH2 in cardiomyocyte H9C2 cells, and activation of ALDH2 can alleviateH O -induced oxidative stress in the cells.</p>