Effect of low-dose ethanol consumption on expression of nuclear factor-κB in diabetic rats with myocardial injury

Abstract

To investigate the effect of low-dose ethanol on the expression of nuclear factor-κB (NF-κB) in diabetic rats with myocardial injury. Rat models of diabetes were established by an intraperitoneal injection of 55 mg/kg streptozotocin (STZ). After successful modeling, the rats were given 2.5% ethanol (daily dose of 20 mg/kg) for 1 week, followed by 5% ethanol (daily dose of 39.45 mg/kg) for another 7 weeks. Normal rats without STZ injection and diabetic rats without ethanol treatment serve as the normal control and diabetic model groups, respectively. The ventricular function of the rats was determined using echocardiography. The plasma levels of interleukin-1 (IL-1) and IL-4 were detected in the rats, and the expressions of 4-HNE, NF-κB and IKK proteins in the left anterior myocardium was evaluated using immunohistochemistry or Western blotting; the ultrastructural changes of the myocardium were observed using transmission electron microscopy. Compared with the normal control group, the diabetic rats showed significantly lowered systolic and diastolic functions of the left ventricle, increased plasma level of IL-1 and myocardial 4-HNE expression (P < 0.01), decreased plasma level of plasma IL-4 (P < 0.01), and increased myocardial expressions of NF-κB and IKK proteins (P < 0.01). Transmission electron microscopy revealed myofibrillar rupture, incomplete myofibrillar structure and mitochondrial damage in the cardiac myocytes in the diabetic rats. Compared with the diabetic rats, the rats with low-dose ethanol treatment exhibited improved systolic and diastolic functions of the left ventricle, milder myocardial myofibrillar and mitochondrial damages, and significantly lowered plasma IL-1 level and myocardial expressions of 4-HNE, NF-κB and IKK (P < 0.01), and increased plasma IL-4 level (P < 0.01). NF-κB expression is increased in the myocardium of diabetic rats with myocardial injury, and low-dose ethanol consumption lowers myocardial expression of NF-κB in diabetic rats, suggesting the involvement of NF-κB signaling pathway in the protective effect of low-dose ethanol against myocardial injury in diabetes mellitus.